多糖对干眼病治疗的临床转化

干眼是一种因泪液分泌不足、蒸发过多或泪液成分异常而引起的一种疾病。主要伴有眼部出现干涩、异物感、畏光、痒感及视物疲劳等症状。重度干眼可引起角膜表层损伤，并可出现角膜浑浊等严重后果。近几年来，随着人们的生活和工作环境的改变，以及环境污染的加剧，智能手机等电子产品的使用率越来越高，干眼病的发病率也在不断增加。目前在临床中，针对干眼的治疗主要采用玻璃酸钠滴眼液，具有良好的亲水性和成膜性，能与纤连蛋白结合，从而促进上皮细胞的连接与伸展，具有很强的保水性，有效地避免了角膜出现干燥，可以很好地缓解干眼病人的症状，但是，单靠药物治疗，疗效并不持久，不能从根本上解决本病。本研究采就中医治疗干眼的研究进展展开探讨，以期为此病的防治提供参考。

干眼是一种由多种原因引起的眼表疾病，近年来其发病率也在升高，对个体及社会都带来了很大的负担。随着人们对干眼发病机制了解的深入，对于干眼的治疗方法也有了更新的进展，本文将通过回顾近年来与干眼药物治疗相关的文献，对干眼药物治疗方面的新进展进行综述。

目的：分析干眼症飞行员泪膜稳定性改变对玻璃酸钠滴眼液临床疗效的影响。方法：选取40例干眼症飞行员，通过泪膜破裂时间(NIKBUT)的检查，将其分为泪膜稳定组和泪膜不稳定组，同时滴用海露(玻璃酸钠)滴眼液，观察治疗前和治疗后其主观症状的变化情况，以评价临床疗效。结果：经7天海露(玻璃酸钠)滴眼液治疗后泪膜稳定组和泪膜不稳定组的眼疲劳症状评分分别为0.97 ± 0.00、1.26 ± 0.49，异物感症状评分分别为1.06 ± 0.13、1.81 ± 0.09，干涩感症状评分分别为0.99 ± 0.20、1.54 ± 0.65。两组比较差异均有统计学意义(P < 0.05)。在泪膜稳定组症状缓解明显。结论：治疗干眼症飞行员时，应常规检查NIKBUT，测定泪膜的稳定性，若泪膜稳定，治疗效果好。有利于考虑是否联合用药和提高治愈率。

目的：分析海露联合重组人表皮生长因子滴眼液对飞行人员干眼症的治疗效果。方法：选取2021年1月~2022年12月于我中心保健疗养的被诊断为干眼症的部队飞行人员120例(240眼)，随机分为观察组与对照组各60例(120眼)，排除眼表其他炎症。对照组给予海露滴眼液治疗，观察组给予海露联合重组人表皮生长因子滴眼液治疗，用药30天，每天四次，每次1滴。结果：治疗后观察组与对照组的显效率分别为91.3%和78.6%，观察组的显效率明显高于对照组(P < 0.05)。治疗后观察组、对照组的非接触泪膜破裂时间(non-invasive break-up time, NIKBUT)分别为(13.36 ± 2.05) s、(10.49 ± 1.23) s，泪河高度(tear meniscus height, TMH)分别为(0.42 ± 0.07) mm、(0.31 ± 0.11) mm，脂质层厚度(Lipid layer thickness, LLT, 0~100 nm)分别为(81.78 ± 5.06) nm、(61.95 ± 6.37) nm。两组比较差异均有统计学意义(P < 0.05)。治疗后观察组、对照组的角膜荧光素染色(fluorescent, FL)评分分别为(0.54 ± 0.19)分、(1.33 ± 0.18)分，存在统计学意义(P < 0.05)。结论：海露联合重组人表皮生长因子滴眼液治疗干眼症能促进泪膜的稳定性，患者主观感觉良好，疗效较好。

目的：系统分析双氯芬酸钠滴眼液联合玻璃酸钠滴眼液与单纯玻璃酸钠滴眼液治疗干眼的临床疗效对比。方法：利用计算机检索PubMed、Cochrane Library、万方数据库、中国知网等数据库，检索文献发表时间从2013-01至2021-01。独立完成对检索到的文献的筛选、评价和数据提取，对治疗后BUT、SIT、FL及干眼症状评分的数据应用Excel软件进行归纳统计，使用RevMan5.4软件完成Meta分析。结果：最终总纳入7篇文献，均为中文文献，共包括患者738例；Meta分析结果显示：双氯芬酸钠滴眼液联合玻璃酸钠滴眼液治疗干眼后能有效延长泪膜破裂时间(BUT) [MD = 2.07, 95% CI (1.06~3.07), P < 0.00001]，联合治疗后的泪液分泌量(Schirmer I test, SIT) [MD = 2.92, 95% CI (1.38~4.47), P < 0.00001]明显优于单纯应用玻璃酸钠滴眼液，并且能降低角膜荧光染色评分/分(FL)以及干眼症状评分。结论：双氯芬酸钠滴眼液联合玻璃酸钠滴眼液在治疗干眼的总体临床疗效上更具优势。

硫酸软骨素(chondroitin sulfate)是天然存在的酸性粘多糖，具有免疫调节、促进伤口愈合、抗病毒作用、抗氧化及调控肿瘤生长等多种药理和生物学活性，并已被广泛用于治疗炎症相关性疾病。此外，还可以作为生物材料应用于医学领域，本综述总结了硫酸软骨素的各种生物学功能及其在疾病治疗中的作用，为进一步临床应用提供了参考。

白及多糖是从中药白及中经过一定工艺提取所得的一种水溶性多糖，又称白及胶，白及多糖作为一种天然高分子载体材料，具有优越的生物相容性、生物粘附性及低毒性等特点，且其本身具有抑菌、抗炎、促凝血、抗肿瘤、免疫调节等生物学活性，使白及多糖在医药领域有很好的开发利用价值。本文就白及多糖的生物学特性及其在医药领域中的应用作一概述，为其后续的开发研究提供理论依据。

研究目的：评估0.05%环孢素A滴眼液每日两次联合0.3%玻璃酸钠滴眼液每日四次连续使用3个月治疗干眼症的疗效。研究方法：门诊纳入符合研究标准的14例干眼患者，使用0.05%环孢素A滴眼液每日2次联合0.3%玻璃酸钠滴眼液每日4次，连续使用3个月。分别在基线、用药后1.5个月和用药后3个月时评估主观症状和客观体征，包括中国干眼问卷量表(CDEQ)、泪液分泌II试验(Schirmer’s II test)、下方角膜荧光素染色评分(ICSS)、荧光素染色泪膜破裂时间(FBUT)、非侵入性平均泪膜破裂时间(NITBUT-av)、泪河高度(TMH)和眼红指数(ORI)，研究结果做自身前后对照。研究结果：连续治疗一个半月后，与用药前相比，CDEQ (P = 0.658)，Schirmer’s II test (P = 0.076)，TMH (P = 0.473)，NTBUT-av (P = 0.211)和ORI (P = 707)数值差异无统计学意义，而FBUT (P = 0.008)和ICSS (P = 0.003)与用药前的差异具有统计学意义。连续治疗三个月后，与用药前相比，CDEQ (P = 0.007)，Schirmer’s II test (P = 0.009)，FBUT (P = 0.008)和ICSS (P < 0.001)的数值差异具有统计学意义，而TMH (P = 0.182)，NTBUT-av (P = 0.080)和ORI (P = 0.337)数值差异无统计学意义。治疗三个月与治疗一个半月时相比，仅有ORI (P = 0.041)的数值差异具有统计学意义。所有患者在治疗过程中，均未出现明显不良反应。研究结论：局部使用0.05%环孢素A滴眼液联合0.3%玻璃酸钠滴眼液，能有效提高干眼症患者的泪膜稳定性并改善主观不适症状。

目的：比较玻璃酸钠滴眼液联合左氧氟沙星滴眼液以及小牛血去蛋白提取物眼用凝胶联合左氧氟沙星滴眼液对角膜异物剔除术后的临床疗效。方法：选取2024年6月至2024年12月在我院行角膜异物剔除术的患者159例，随机分为玻璃酸钠滴眼液组80例和小牛血去蛋白提取物眼用凝胶组79例。两组分别给予玻璃酸钠滴眼液联合左氧氟沙星滴眼液治疗和小牛血去蛋白提取物眼用凝胶联合左氧氟沙星滴眼液治疗，比较两组患者的术后恢复情况。结果：玻璃酸钠滴眼液组80例中痊愈63例，好转17例，无效0例，痊愈率78.8%，有效率100%；小牛血去蛋白提取物眼用凝胶组79例中痊愈70例，好转9例，无效0例，痊愈率86.1%，有效率100%，两组痊愈率比较，差异有统计学意义(P < 0.05)。结论：玻璃酸钠滴眼液和小牛血去蛋白提取物眼用凝胶与左氧氟沙星滴眼液联合使用，对角膜异物剔除术后的眼部恢复均有效，其中使用小牛血去蛋白提取物眼用凝胶效果更佳，痊愈率更高。

目的：评价调神润目针法结合人工泪液治疗干眼症的临床效果。方法：前瞻性选取2024年1月至2024年10月于黑龙江中医药大学附属第二医院针灸二科就诊的干眼症患者70例，采用随机数字表法分为针药组和药物组，每组35例。针药组采用调神润目针法联合人工泪液治疗，药物组单纯使用人工泪液。疗程为每日1次，连续治疗2周。比较两组治疗前后的眼表疾病指数(OSDI)、泪膜破裂时间(BUT)、泪液分泌试验(SIT)、角膜荧光素染色(FL)及泪河高度(TMH)等指标，评估临床疗效。结果：两组患者治疗前OSDI、BUT、SIT、FL、TMH基线水平无统计学差异(P > 0.05)。治疗后两组OSDI评分均下降，且针药组显著低于药物组(P < 0.05)。治疗后BUT、SIT、FL、TMH均显著增加，且针药组改善程度明显优于药物组(P < 0.05)。针药组临床总有效率显著高于药物组，差异具有统计学意义(P < 0.05)。结论：调神润目针法结合人工泪液治疗干眼症能够有效改善患者的眼部症状，促进泪液分泌，稳定泪膜状态，临床疗效显著优于单纯人工泪液治疗。

我国是一个近视大国，许多近视患者想摆脱眼镜的困扰选择了屈光手术，角膜屈光术后干眼通常是暂时的，但会造成不规则散光，诱发高阶像差，造成患者术后视觉质量和手术满意度下降。本文就角膜屈光术后干眼的发病机制、治疗研究进展进行综述，以期屈光医师对有干眼症风险的患者采取预防措施，对角膜屈光术后干眼患者治疗提供依据。

目的：介绍眼部给药系统及其体内评价方法的进展。结果：通过查阅总结近年来眼部给药系统及其体内评价方法的国内外文献报道，总结发现近年来新型眼部给药系统有凝胶系统、胶粒系统、环糊精包合物等，其体外评价方法主要为体外释放实验，其体内评价方法主要包括眼部滞留时间和药动学研究。结论：新型眼部给药系统及其体内外评价方法都有较大的进展，虽然还存在一定的不足，但均具有很好的发展前景。

硫酸软骨素(chondroitin sulfate, CS)是一种天然糖胺聚糖(glycosaminoglycan，GAG)，具有多重药理作用及结构可塑性。作为一类生物多糖，CS除了具有抗炎、抗肿瘤、促进细胞再生、抗病毒等生物活性外，其本身也作为生物材料在医学领域，如眼科、骨科、肿瘤等方向广泛应用。本文针对CS在病理生理与免疫系统中的生物学特性，及其在药物输送系统和组织工程中的应用进行概述，为其后续的开发研究提供理论依据。

干眼症是一种常见的眼科疾病，严重影响患者的生活质量和视力。随着对干眼症病理生理机制的深入研究，学术界不断探索新的治疗策略。近年来，新型药物的研发、物理治疗方法的改进、干细胞疗法的应用以及创新设备的开发等多种前沿治疗策略相继提出，展现出良好的临床应用前景。现有治疗手段在一定程度上缓解了干眼症的症状，但仍存在疗效不稳定、副作用及个体差异等问题。本文旨在综述干眼症的最新治疗动态，分析当前治疗现状中所面临的挑战，并展望未来可能的研究方向，以期为临床医生和研究者提供有价值的信息，推动干眼症的诊疗进步。

药物缓释剂可以减少病人的给药次数，还使病人体内药物浓度稳定，使患者易于耐受。水凝胶具有良好的生物相容性和生物可降解性，适于作为药物缓释的药物载体。本文不仅阐述了水凝胶在药物控制释放体系方面的优势，而且概述了不同制备方法对应水凝胶在药物缓释上的应用。除此之外，本文还阐述了新型的水凝胶搭载疏水性药物的方法。

Purpose To evaluate the safety and efficacy of Lycium barbarum polysaccharide (LBP) eye drops in a murine model of dry eye disease (DED). Methods Six- to eight-week-old female C57BL/6 mice were subjected to a combination of desiccating stress (DS) and topical benzalkonium chloride (BAC) to induce DED. Five microliters of LBP eye drops (0.625, 2.5, or 12.5 mg/ml) or PBS was applied topically 3 times per day for 10 days to subsequently test their efficacy. Tear secretion, tear breakup time (TBUT), corneal irregularity, and corneal fluorescein staining scores were measured on days 3 and 10 after treatment. The expression of tumor necrosis factor-alpha (TNF-α) in the cornea was assessed by quantitative (q) RT–PCR on days 10. The ocular irritation of LBP eye drops of corresponding concentrations was evaluated on 10- to 12-week-old female Sprague–Dawley rats. Results Compared with PBS-treated groups, mice treated with 0.625, 2.5, and 12.5 mg/ml LBP showed a significant improvement in the clinical signs of DED in a dose-dependent manner, including corneal epithelial integrity, corneal regularity, and tear production, as well as significant inhibition of inflammatory cell infiltration and TNF-α expression levels in the cornea. All corresponding concentrations of LBP eye drops revealed no obvious ocular irritation. Conclusion Topical application of LBP could ameliorate dry eye in a murine model of DED without obvious ocular irritation.

Dry eye disease (DED) is a multifactorial condition of the ocular surface, primarily treated with tear substitutes, which do not fully restore natural tear functions. In this pilot study, we tested the hypothesis that T-Lysyal (T-Lys) improves symptoms and signs in patients with DED. Additionally, we provide a literature overview on the effects of T-Lys in ophthalmology and non-ophthalmology conditions to elucidate its mechanisms of action. A double-masked, randomized pilot study was conducted in patients with DED treated with T-Lys or hyaluronic acid (HA) 0.2% combined with tamarind seeds polysaccharide (control group) for 2 months. Inclusion criteria were a diagnosis of DED with symptoms lasting ≥ 6 months, Symptom Assessment in Dry Eye (SANDE) score ≥ 30, and at least one of the following: fluorescein staining of the cornea (score ≥ 3, NEI scale), conjunctival staining (Lissamine Green, score ≥ 3), or tear breakup time (T-BUT) ≤ 10 s. Data from the right eye were used for statistical analysis. A PubMed literature search of T-Lys studies was also performed without publication year restrictions. Twelve patients in the T-Lys group and 15 in the control group completed the study (mean age 67 ± 11 years). T-Lys treatment resulted in significant improvements from baseline (V0) to 2 months (V2) in symptoms assessed by visual analogue scale (T-Lys: 4.58 ± 2.57 mm at V0, 2.92 ± 1.38 mm at V2, p < 0.05; control: 5.13 ± 2.29 mm at V0, 5.3 ± 2.4 mm at V2), T-BUT (T-Lys: 2.58 ± 1.31 s at V0, 3.58 ± 1.37 s at V2, p < 0.05; control: 3.07 ± 1.43 s at V0, 3 ± 1.13 s at V2), and corneal staining (T-Lys: 2.16 ± 4.17 at V0, 1.41 ± 3.70 at V2, p < 0.05; control: 1.4 ± 2.19 at V0, 1.4 ± 2.16 at V2). No adverse events were reported. Literature findings supported T-Lys’s efficacy in managing both ophthalmology and non-ophthalmology conditions. This study provides the first clinical evidence of T-Lys efficacy in patients with DED, supporting preclinical data and highlighting its potential as a promising ocular surface modulator. The study was registered in the ISRCTN registry for Clinical Studies with no. 13587929.

No abstract available

Hyaluronic acid (HA) is a naturally occurring polysaccharide with many molecular functions, including maintaining the structure and physiology of the tissues, tissue remodeling, and inflammation. HA is found naturally in physiological tear fluid, possesses excellent mucus-layer-adhesive properties, and is successfully employed in the treatment of dry eye syndrome (DES). However, HA has as major drawback: its rapid in vivo degradation by hyaluronidase. We report on a unique material, namely, HA-3, obtained by the functionalization of HA with the metalloproteinase inhibitor 3 (MMPI). This material is characterized by an increased resistance to hyaluronidase degradation, associated with MMP inhibition properties. The ability of HA-3 to prevent dehydration of human corneal epithelial cells in vitro and in vivo may accelerate the development of more efficient DES treatment and broaden the application of HA in human diseases.

Dry eye syndrome (DES) is a multifactorial disorder of the ocular surface affecting many people all over the world. However, there have been many therapeutic advancements for the treatment of DES, substantial long-term treatment remains a challenge. Natural plant-based polysaccharides have gained much importance in the field of tissue engineering for their excellent biocompatibility and unique physical properties. In this study, polysaccharides from a Chinese ground orchid, Bletilla striata, were successfully extracted and incorporated into the artificial tears for DES treatment due to its anti-inflammatory and mucoadhesive properties. The examination for physical properties such as refractive index, pH, viscosity and osmolality of the Bletilla striata polysaccharide (BSP) artificial tears fabricated in this study showed that it was in close association with that of the natural human tears. The reactive oxygen species (ROS) level and inflammatory gene expression tested in human corneal epithelium cells (HCECs) indicated that the low BSP concentrations (0.01–0.1% v/v) could effectively reduce inflammatory cytokines (TNF, IL8) and ROS levels in HCECs, respectively. Longer retention of the BSP-formulated artificial tears on the ocular surface is due to the mucoadhesive nature of BSP allowing lasting lubrication. Additionally, a rabbit’s DES model was created to evaluate the effect of BSP for treating dry eye. Schirmer test results exhibited the effectiveness of 0.1% (v/v) BSP-containing artificial tears in enhancing the tear volume in DES rabbits. This work combines the effectiveness of artificial tears and anti-inflammatory herb extract (BSP) to moisturize ocular surface and to relieve the inflammatory condition in DES rabbit, which further shows great potential of BSP in treating ocular surface diseases like DES in clinics in the future.

BackgroundOne of the problems arising from available preparations for dry eye syndrome is the limited residence time of products on the ocular surface. In this paper, we look at an innovative new treatment for dry eye, tamarind seed polysaccharide (TSP). TSP possesses mucomimetic, mucoadhesive and pseudoplastic properties. The 'mucin-like' molecular structure of TSP is similar to corneal and conjunctival mucin 1 (MUC1), a transmembrane glycoprotein thought to play an essential role in protecting and wetting the corneal surface and may explain its increased retention on the eye surface.MethodsThe activity of TSP and hyaluronic acid (HA) in the treatment of dry eye syndrome was compared in an open-label, randomised, single-centre clinical study. Thirty patients were randomised to receive three or more applications per day of either TSP 0.5%, TSP 1% or HA 0.2% (Hyalistil™) over a period of 90 days. The primary objective of tolerability was assessed by visual analogue scale (VAS), scoring of specific symptoms and the incidence of adverse events. Secondary objectives included improvement in stability of the precorneal tear film, subjective symptoms and corneal and conjunctival staining.ResultsTSP 0.5% and 1% were comparable to HA 0.2% with regard to both primary and secondary objective parameters.TSP 1% showed benefits over HA 0.2% for the subjective symptoms; trouble blinking, ocular burning and foreign body sensation.ConclusionThis study suggests that TSP 0.5% and 1% offer at least equivalent relief to HA 0.2% for dry eye syndrome. All treatments demonstrated optimal tolerability and are suitable for frequent use in the therapy of dry eye.TSP 1% produced promising results in terms of improvements in certain patient symptoms and suggests benefits of the TSP formulation. This study paves the way for a larger study to further establish the performance and safety of TSP compared with HA and highlights the need to expand this therapeutic agent to a wider dry eye population.

Background The enhancement of ocular drug delivery is achieved by using biopolymer carriers in liquid ophthalmic preparations. Using natural polysaccharides to formulate ocular medications is attractive because they are economical and readily available. The primary goal of the study was to assess the safety and effectiveness of Tamarind seed polysaccharide (TSP)/Hyaluronic acid (HA) containing Rohto eye drops (TSP/HA drops) in alleviating the signs and symptoms of dry eye disease (DED) under dry environmental conditions using controlled environmental chamber (CEC). Methods 12 participants were subjected to harsh environmental conditions in a CEC with a relative humidity (RH) of 5% and an ambient temperature of 21°C. TSP/HA drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment and relief (drops instilled after exposure to the dry environment. Before and after administering drops, patients undergo screening for ocular symptoms, tear osmolarity, ocular surface temperature (OST), and tear production using the ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and phenol red test (PRT) respectively. Tear production was calculated by the Tear Function Index test (TFI). Results Before (protection) and after (relief) exposure to the dry environment, TSP/HA resulted in a mean tear osmolarity of 296.0 mOsm/L and 292.0 mOsm/L, with no significant statistical difference. The presence of TSP/HA in both protection and relief modes led to an increase in tear production. TSP/HA drops did not significantly affect OST compared to the absence of TSP/HA drops at 5% RH. There was a significant increase in mean symptom score from 14 at 40% RH to 128 at 5% RH (p=0.003). A substantial reduction in symptoms was found in both protection (before exposure) (35) (p=0.003) and relief (after exposure) (50) (p=0.005) compared to when no drop was used. Conclusion It was apparent that using TSP/HA for protection was superior to relief for osmolarity and eye comfort. To optimise the therapeutic efficacy of TSP/HA, it is advisable to instruct patients to administer it before exposure to dry atmospheric conditions. The small sample size limits the ability to generalize the findings. Future studies should evaluate the tear supplement with a larger sample to improve statistical power.

Dry eye is a common disorder in routine ophthalmological practice, and a better understanding of the complex pathophysiology is leading to improved treatment. Thealoz Duo® is a novel artificial tear preparation containing two active ingredients: Trehalose, a naturally occurring disaccharide with anhydrobiotic functions in many organisms, and hyaluronate, a widely distributed anionic glycosaminoglycan polysaccharide with lubricative and water-retaining properties in biological systems. In a randomized, single center, open label, crossover study, 17 adult patients with moderate-to-severe dry eye syndrome were randomized to treatment with Thealoz Duo® (combining trehalose and hyaluronic acid) or Systane®. Patients received 7 days of treatment. The primary efficacy variable was patient satisfaction evaluated by a 0–100 visual analog scale evaluated on days 0 and 7 of treatment. Secondary parameters included ocular surface disease index (OSDI), symptoms of dry eye, ocular staining scores (fluorescein and lissamine green), ocular clinical signs, Schirmer test, tear breakup time, and global efficacy assessed by the patient and the investigator. Seventeen patients were included. Patient satisfaction improved from 44.5±19.0 to 70.2±19.2 mm during Thealoz Duo® treatment and from 47.2±23 to 57.1±19.1 mm during Systane® treatment (P=0.043, mixed-effects analysis of covariance). Two secondary efficacy parameters (dry eye symptoms and the impact of their symptoms on work) showed statistically significant advantages for Thealoz Duo® over Systane®. There were no statistically significant advantages for Systane® over Thealoz Duo® for any measured parameter. No adverse events were reported. Thealoz Duo® appears to be an effective combination of two active ingredients for the treatment of dry eye and is at least as effective as Systane®.

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Hyaluronic acid (HA) has been commonly used in eyedrop formulations due to its viscous lubricating properties even at low concentration, acting as a supplement for ocular mucin (principally MUC5AC) which diminishes with aging in a condition known as Keratoconjunctivitis sicca or “dry eye”. A difficulty has been its short residence time on ocular surfaces due to ocular clearance mechanisms which remove the polysaccharide almost immediately. To prolong its retention time, tamarind seed gum polysaccharide (TSP) is mixed as a helper biopolymer with HA. Here we look at the hydrodynamic characteristics of HA and TSP (weight average molar mass Mw and viscosity η) and then explore the compatibility of these polymers, including the possibility of potentially harmful aggregation effects. The research is based on a novel combination of three methods: sedimentation velocity in the analytical ultracentrifuge (SV-AUC), size-exclusion chromatography coupled to multiangle light scattering (SEC-MALS) and capillary viscometry. HA and TSP were found to have Mw=(680±30) kg/mol and (830±30) kg/mol respectively, and η=1475±30 ml/g and 675±20 ml/g, respectively. The structure of HA ranges from a rodlike molecule at lower molar masses changing to a random coil for Mw > 800 kg/mol, based on the Mark–Houwink–Kuhn–Sakurada (MHKS) coefficient. TSP, by contrast, is a random coil across the range of molar masses. For the mixed HA-TSP systems, SEC-MALS indicates a weak interaction. However, sedimentation coefficient (s) distributions obtained from SV-AUC measurements together with intrinsic viscosity demonstrated no evidence of any significant aggregation phenomenon, reassuring in terms of eye-drop formulation technology involving these substances.

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A structural conjugate (HOC) of polysaccharide, hyaluronic acid (HA) with different ratios of oleic acid (OA) via cystamine (CYS) linker as a new ocular biomaterial was developed. The HOCs with controlled degrees of substitution of OA (4.6 %, 8.3 % and 12.2 %) were synthesized to form self-assembled HA-CYS-OA nanoparticles (HONs, HON1, HON2, HON3). A poorly water-soluble cyclosporine A (CsA) to be used for the treatment of multifactorial dry eye disease (DED) was chosen as model drug. CsA-loaded HONs exhibited improved solution transparency via solubilizing capacity of HON, and increased in vitro drug permeation compared to Restasis®. The physicochemical properties of CsA-loaded HONs such as nano behaviors, solution transparency, drug release, drug permeation and ocular cytocompatibility were highly variable according to the ratios of OA substitution. Interestingly, this CsA-loaded HON1 as optimal ocular nanoformulation showed markedly augmented macrophage polarization into the M2 phenotype, downregulated the expression of proinflammatory cytokines levels in LPS-induced M1 macrophage, and effectively inhibited VEGF-induced endothelial cell proliferation and capillary-like tube formation by the synergistic effect of CsA and HON1 containing OA at the same time. Collectively, the current fatty acid conjugated to HA, named fattigation platform, providing the roles and physicochemical properties via structural features of HA could be a promising co-delivery strategy of drug and fatty acid for DED and other ophthalmic disease treatments.

Disruption of the epithelial barrier function has been recently associated with a variety of diseases, mainly at intestinal level, but also affecting the respiratory epithelium and other mucosal barriers. Non-pharmacological approaches such as xyloglucan, with demonstrated protective barrier properties, are proposed as new alternatives for the management of a wide range of diseases, for which mucosal disruption and, particularly, tight junction alterations, is a common characteristic. Xyloglucan, a natural polysaccharide derived from tamarind seeds, possesses a “mucin-like” molecular structure that confers mucoadhesive properties, allowing xyloglucan formulations to act as a barrier capable of reducing bacterial adherence and invasion and to preserve tight junctions and paracellular flux, as observed in different in vitro and in vivo studies. In clinical trials, xyloglucan has been seen to reduce symptoms of gastroenteritis in adults and children, nasal disorders and dry eye syndrome. Similar mucosal protectors containing reticulated proteins have also been useful for the treatment of irritable bowel syndrome and urinary tract infections. The role of xyloglucan in other disorders with mucosal disruption, such as dermatological or other infectious diseases, deserves further research. In conclusion, xyloglucan, endowed with film-forming protective barrier properties, is a safe non-pharmacological alternative for the management of different diseases, such as gastrointestinal and nasal disorders.

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler’s TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50–70 nm (grade 3) at 40% RH to 10–50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments.

Riboflavin under UVA radiation generates reactive oxygen species (ROS) that can induce various changes in biological systems. Under controlled conditions, these processes can be used in some treatments for ocular or dermal diseases. For instance, corneal cross-linking (CXL) treatment of keratoconus involves UVA irradiation combined with riboflavin aiming to induce the formation of new collagen fibrils in cornea. To reduce the damaging effect of ROS formed in the presence of riboflavin and UVA, the CXL treatment is performed with the addition of polysaccharides (dextran). Hyaluronic acid is a polysaccharide that can be found in the aqueous layer of the tear film. In many cases, keratoconus patients also present dry eye syndrome that can be reduced by the application of topical solutions containing hyaluronic acid. This study presents physico-chemical evidence on the effect of riboflavin on collagen fibril formation revealed by the following methods: differential scanning microcalorimetry, rheology, and STEM images. The collagen used was extracted from calf skin that contains type I collagen similar to that found in the eye. Spin trapping experiments on collagen/hyaluronic acid/riboflavin solutions evidenced the formation of ROS species by electron paramagnetic resonance measurements.

PURPOSE To investigate the prognostic ability of blink rate and the proportion of incomplete blinking to predict dry eye disease diagnosis, as defined by the TFOS DEWS II criteria. METHODS A total of 453 community residents (282 females, 171 males; mean ± SD age, 37 ± 19 years) were recruited in an investigator-masked, prospective registry-based, cross-sectional, prognostic study. Dry eye symptomology, tear film quality, and ocular surface characteristics were assessed in a single clinical session, and blink parameters evaluated by an independent masked observer. RESULTS Overall, 214 (47 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease. Multivariate regression analysis demonstrated that an increased proportion of incomplete blinking was associated with a higher odds of dry eye disease (odds ratio, 1.12 per 10 % increase; 95 % CI, 1.05-1.19; p < 0.001), with the Youden-optimal prognostic threshold proportion being ≥ 40 % incomplete blinking. Higher levels of incomplete blinking were also associated with poorer dry eye symptomology, tear film stability, corneal and lid margin staining, lipid layer thickness, meibography, and meibum quality (all p ≤ 0.03). No significant associations were detected between blink rate and ocular surface parameters (all p > 0.10). CONCLUSIONS The degree of incomplete blinking is a significant predictor of dry eye disease, and the utility of incorporating blink assessment into diagnostic workup algorithms warrants further investigation. The association with meibomian gland dropout, expressed meibum quality, and lipid layer thickness would suggest that incomplete blinking may predispose towards the development of meibomian gland dysfunction.

Managing Dry Eye Disease (DED), a prevalent condition affecting the ocular surface, remains challenging despite advancements in diagnostics and therapies. Current treatments primarily involve lubricating eye drops and anti-inflammatory medications, which often require prolonged use and generally provide only symptomatic relief. The current study focuses on improving DED treatments through nano-drug delivery technologies and advanced formulations. These systems aim to address the limitations of conventional therapies by providing extended, targeted, and sustained drug release. The development of innovative nanomaterials offers improved precision, control, and customization for DED management. By enabling controlled and sustained drug release, these nano-drug delivery systems could offer longer-lasting relief, addressing the chronic nature of DED more effectively than current symptomatic therapies. Future research should focus on integrating multiple therapeutic agents within these systems to simultaneously target inflammation and tear film instability. This review examines the potential of nano-based materials for DED treatment, with a particular emphasis on lipid-based, polymer-based and polysaccharide-based systems.

Purpose Report the clinical effects and discomfort of using 0.1% hyaluronic acid (HA [Kynex 1®, Alcon, Seoul, S. Korea]) and 0.3% HA (Kynex 3®, Alcon, Seoul, S. Korea) to treat dry eye disease (DED). Methods This study was designed as a prospective, crossover, randomized, and double-blind study. Patients aged >19 years with DED level 2 or higher, corneal staining score > 1, and tear break-up time (TBUT) < 10s were included. Sixty patients were randomly assigned to two groups. Patients in group 1 were instilled with 0.1% HA for four weeks and then 0.3% HA for the next four weeks. Group 2 patients were instilled with the eye drops in the reverse order of group 1. Patients were evaluated using a corneal staining score, TBUT, and the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire at baseline, four weeks, and eight weeks. Results In both groups, 0.3% HA showed an increasing trend in TBUT, although the difference was not statistically significant. Changes in the Schirmer test were greater in group 2, but this difference was also not statistically significant. The corneal staining score improved in both groups, with no statistically significant difference. While 0.3% HA was more effective than 0.1% HA according to the absolute value, this difference was not statistically significant. There was no difference between the two groups in the SPEED questionnaire evaluation that assessed aspects of discomfort, such as blurred vision, foreign body sensation, and burning sensation. Conclusion 0.3% HA was more effective for treating DED, although the difference was not statistically significant. In terms of discomfort, 0.3% HA showed no difference compared to 0.1% HA. Using both 0.1% HA and 0.3% HA in a tailored treatment approach can improve patient comfort and treatment outcomes.

Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo®, T/HA) with a tear substitute containing 0.001% hydrocortisone (I) and 0.2% HA (Idroflog®, I/HA), with respect to changes on signs and inflammatory markers in a mouse DED model. Methods: Thirty 12-week-old C57BL/6 mice were exposed in a controlled-environment chamber as a desiccating stress model of DED for 35 days. At day 14 (T1), administration of 5 µL T or I in the right eye (RE) or NaCl 0.9% in the left eye (LE) started, twice a day. Animals were sacrificed after 7 (T2), 14 (T3), 21 (T4, endpoint) days from the beginning of treatment. Corneal fluorescein staining ratio (Image J), histological and histochemical assessment of ocular surface tissues (goblet cell GC density and characterization —PAS, Alcian blue pH 2.5, pH 1.0, and MUC4 expression—in the superior and inferior conjunctiva), and levels of inflammatory markers HLA-DR, IL-1β and TNF-α in cornea and conjunctiva were measured. Results: No animal fully recovered from DED signs at the endpoint. Difference between arms was observed at T3 and T4, with T treated eyes showing a higher corneal damage reduction, PAS-positive GC recovery, lower inflammatory marker expression as compared to the I treated ones. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA.

Background The global prevalence of diabetes mellitus (DM) continues to rise and 70% of diabetic individuals have dry eye disease (DED) that leads to subsequent abnormalities of the corneal epithelium, corneal nerves, tear film, or corneal endothelium. In addition, persons with diabetes produce fewer tear secretions than healthy individuals. While several anti-inflammatory drug-based therapies for dry eye in diabetic individuals are currently being administered, their efficacy has not been studied in detail. Therefore, the aim of this study was to compare the effectiveness of 3% diquafosol (DQS) vs 0.1% hyaluronic acid (HA) eye drops in diabetic dry eye patients. Methods This triple-blind randomized, control trial will include 202 diabetic-related DED and will be assigned to DQS ( n = 101) and HA ( n = 101) one drop, six times per day for 8 weeks. Tear film lipid layer, non-invasive breakup time, conjunctivocorneal staining score, corneal sensitivity, tear MMP-9 levels, meibomian gland expression and quality, tear meniscus height, corneal nerves, immune/inflammatory cell change, conjunctival hyperemia, and ocular surface disease index questionnaire score will be assessed and compared at baseline, week 4, and week 8. Discussion This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of DQS and HA for diabetic dry eye treatment. Trial registration ClinicalTrials.govNCT05682547. Registered on December 05, 2022.

Introduction The number of cataract surgeries, the most common ophthalmic surgery, is expected to increase due to ageing populations. Dry eye disease (DED) is a frequent side effect of cataract surgery, contributing to lower postoperative patient satisfaction and suboptimal quality of vision. It is unclear which eye-drops commonly used in these patients should be recommended for postoperative DED treatment. This study aims to compare the efficacy of topical administration of diquafosol sodium 3% vs hyaluronic acid 0.1% eye-drops in patients with DED after cataract surgery. Methods and analysis The study is designed as a single-blind randomised controlled trial. The participants will be randomly (1:1) allocated to either the diquafosol sodium 3% topical administration group (n=21) or the hyaluronic acid 0.1% topical administration group (n=21). Each group will receive its assigned eye-drop intervention over a 12-week period. The primary outcome will be measured using the total score of the Japanese version of the Ocular Surface Disease Index during the visit 5 weeks postoperatively. Both groups will be followed up after their respective eye-drop application for 12 weeks according to the intervention regimens. Secondary outcome measures including meibomian gland function assessment, tear film break-up time, keratoconjunctival staining score, maximum blink interval and tear secretion volume using Schirmer’s test I will be assessed at 1, 5, 9, 13 and 25 weeks postoperatively. Ethics and dissemination This study has been approved by the Juntendo Hospital Certified Review Board, Tokyo, Japan (Approved protocol V.7.0 dated 7 May 2021. Approval number: J20-018) and has been registered with the Japan Registry of Clinical Trials. Written informed consent will be collected from every patient prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication. Trial registration number jRCT1031210018.

Purpose: To evaluate the prevalence of dry eye disease (DED) after cataract surgery, and the impact of hyaluronic acid and ginkgo biloba eyedrops (HA-GB). Methods: Forty patients with no DED received Ocular Surface Disease Index (OSDI) questionnaire, assessment of conjunctival hyperemia and epithelial damage, fluorescein tear break-up time (TBUT) at baseline, day 1, week 1, and 4; adherence and tolerability were checked at weeks 1 and 4. At day 0 patients underwent cataract surgery and were randomized to standard postoperative care (control group) or standard postoperative care + HA-GB 3 times a day for 4 weeks (HA-GB group). Results: At baseline, TBUT was 9.6 ± 2.6 sec in controls and 9.0 ± 1.6 in HA-GB; thereafter it was higher in HA-GB group: 5.8 ± 2.3 versus 7.8 ± 3.2 (week 1, P = 0.03) and 6.4 ± 2.3 versus 8.5 ± 2.5 (week 4, P = 0.009). OSDI and conjunctival hyperemia were better in HA-GB group at week 4; respectively, 9.0 ± 5.7 versus 14.8 ± 7.3 (P = 0.004) and 5% versus 35% (P = 0.04). In the last 2 visits 50% of controls were symptomatic (OSDI of 13 or higher) compared with 16% on HA-GB group (P < 0.001). In addition, tolerability was higher in HA-GB group (week 1: 0.81 ± 0.20 versus 0.70 ± 0.24, P = 0.007; week 4: 0.93 ± 0.17 versus 0.80 ± 0.28, P = 0.001). Conclusion: Treatment with HA-GB is effective in reducing DED signs and symptoms in patients receiving cataract surgery, with high tolerability and safety profiles. clinicaltrials.gov (ID number NCT05002036).

Purpose To assess the efficacy, adherence, and tolerability of a new artificial tear based on arabinogalactan, hyaluronic acid, and trehalose in a population with dry eye disease (DED). Methods A retrospective, real-world, post-marketing study identified 96 adult patients (aged 18–80 years) with signs and symptoms of dry eye. These patients received fixed combination therapy with eye drops containing arabinogalactan, hyaluronic acid, and trehalose at various dosing schedules. The data for this study were collected from April 2022 to June 2023. Patients underwent evaluation at baseline (T0) and after a follow-up period of two–three months (T1) using a patient-reported questionnaire. Results In 96 adult patients (71 women and 25 men) with dry eye due to various conditions, the results indicated a 98% positive response to therapy. This response included improvements in vision (13%), comfort (39%), redness (13%), itching (16%), photophobia (4%), and tearing (14%). Additionally, 61% of the patients experienced 1–2 hours of comfort following instillation. Conclusion This real-life post-marketing study demonstrated clinical improvement of signs and symptoms in patients with dry eye disease using a new artificial tear medical device based on arabinogalactan, hyaluronic acid, and trehalose.

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Objectives: Topical lubricants are the fundamental treatment for dry eye disease (DED). However, the molecular mechanisms underlying their efficacy remain unknown. Here, the protective effects of Thealoz® Duo with 3% trehalose and 0.15% hyaluronic acid are investigated in DED patients by a longitudinal clinical study and subsequent elucidation of the tear proteome and cell signaling changes. Methods: Participants were classified as moderate to severe DED (DRY, n = 35) and healthy (CTRL, n = 23) groups. Specific DED subgroups comprising evaporative (DRYlip) and aqueous-deficient with DRYlip (DRYaqlip) were also classified. Only DED patients received Thealoz® Duo. All participants were clinically examined before (day 0, T1) and after the application of Thealoz® Duo at day 28 (T2) and day 56 (T3). Next, 174 individual tear samples from all groups at three time-points were subjected to proteomics analysis. Results: Clinically, Thealoz® Duo significantly improved the ocular surface disease index at T2 vs. T1 (DRY, p = 1.4 × 10−2; DRYlip, p = 9.2 × 10−3) and T3 vs. T1 (DRY, p = 2.1 × 10−5; DRYlip, p = 1.2 × 10−4), and the tear break-up time at T3 vs. T1 (DRY, p = 3.8 × 10−2; DRYlip, p = 1.4 × 10−2). Thealoz® Duo significantly ameliorated expression of inflammatory response proteins (p < 0.05) at T3, which was observed at T1 (DRY, p = 3.4 × 10−4; DRYlip, p = 7.1 × 10−3; DRYaqlip, p = 2.7 × 10−8). Protein S100-A8 (S100A8), Alpha-1-antitrypsin (SERPINA1), Annexin A1 (ANXA1), and Apolipoprotein A-I (APOA1) were found to be significantly reduced in all the DED subgroups. The application of Thealoz® Duo showed the therapeutic characteristic of the anti-inflammatory mechanism by promoting the expression of (Metalloproteinase inhibitor 1) TIMP1 in all the DED subgroups. Conclusions: Thealoz® Duo substantially improved the DED symptoms and restored the functionality of the tear lipid layer to near normal in DRYlip and DRY patients by ameliorating inflammation. Notably, this study unravels the novel mechanistic alterations underpinning the healing effects of Thealoz® Duo in DED subgroups in a time-dependent manner, which supports the improvement in corresponding clinical attributes.

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Background: Dry eye disease (DED) is a prevalent complication following phacoemulsification surgery, especially among diabetic patients who are predisposed due to metabolic and vascular changes. Tear film instability, ocular inflammation, and delayed epithelial healing contribute to persistent postoperative discomfort and impaired vision. Identifying effective interventions is critical for enhancing visual rehabilitation and patient quality of life. This study compared the effectiveness of hyaluronic acid (HA) and lipid-coated carbomer gel (LCC) in improving tear film stability and alleviating dry eye symptoms in diabetic patients after cataract surgery. Objective: To evaluate and compare the efficacy of HA and LCC in diabetic patients with postoperative DED using Tear Break-Up Time (TBUT) and Schirmer’s Test. Methods: A randomized clinical trial was conducted at Shaheen Welfare Hospital, Lahore, including 64 diabetic patients aged 50–70 years who developed DED after uncomplicated phacoemulsification. Participants were randomized into two equal groups: Group A received HA drops, and Group B received LCC gel for four weeks. Data were collected at baseline, 2 weeks, and 4 weeks using TBUT and Schirmer’s Test. Randomization was computer-generated, blinding was maintained, and SPSS version 25 was used for statistical analysis. Mann–Whitney and Friedman tests determined between- and within-group differences, with significance set at p<0.05. Results: At baseline and at the 2nd week, no significant difference was observed between groups in TBUT or Schirmer’s Test (p=1.000). At the 4th week, LCC demonstrated significant superiority. Mean ranks for TBUT were 41.27 in the LCC group versus 23.73 in the HA group (p=0.000). For Schirmer’s Test, LCC showed a mean rank of 46.63 compared to 18.38 for HA (p=0.000). Within-group analysis confirmed progressive improvement in both groups, though LCC achieved higher scores consistently by week 4. Conclusion: Lipid-coated carbomer gel demonstrated superior efficacy over hyaluronic acid in improving tear film stability and tear secretion among diabetic patients with postoperative dry eye disease. These findings suggest LCC as a more effective and preferable option for managing moderate to severe DED after cataract surgery.

Topical instilling of commercial artificial tears (cAT, containing 0.1 % hyaluronic acid) is widely employed to alleviate clinical manifestations of mild dry eye disease (DED) by preventing the pathological change of corneal epithelium. However, it showed limited therapy effectiveness on heavy DED which has further involved corneal stroma, due to its low stroma-available for hyaluronic acid (HA) resulting from the barrier of corneal epithelium. The present study developed a new microneedle-dosage form of cAT (cAT-MN). This cAT-MN can overstride the corneal epithelium and act as a long-lasting protective agent. Compared to cAT dosing (4 times/day), cAT-MN with one treatment exerted significantly higher therapeutic effects on curbing benzalkonium chloride (BAC)-induced corneal stroma scaring as well as alleviating the DED symptoms in the first 5-day BAC exposure; whereas, showed limited effects in a 10-day BAC exposure. To expand the therapy effects, MNs containing various amounts of HA were prepared. Thereinto, HA(6 %)-MN recovered corneal damage to healthy levels, which could be attributed to adding stroma-available for HA both by increasing the amounts of HA-delivery and enhancing HA-permeation. This study explores a new drug-free microneedle-dosage form of cAT to cure corneal stroma disorders which has expanded its indication, promising a wide clinical use in ophthalmology.

PURPOSE To assess the clinical efficacy and safety of T2769, a new preservative-free eye drop combining hyaluronic acid (HA), trehalose and N-acetyl-aspartyl-glutamic acid (NAAGA), in dry eye patients. PATIENTS AND METHODS This was a multicenter, non-comparative, open-label study. After a run-in period with NaCl 0.9% solution, 62 patients with moderate-to-severe dry eye disease (DED) were included and treated with T2769, 3 to 6 times/day for 42 days. The primary efficacy endpoint was the change in global ocular symptomatology assessed on a visual analog scale between Day 1 (D1) and D42. Other efficacy endpoints included ocular surface disease index (OSDI), soothing sensation, individual dry eye symptoms, conjunctival hyperemia, global ocular staining, tear break-up time, Schirmer test, and global efficacy assessed by the investigator. Safety was assessed throughout the study. RESULTS A marked reduction in ocular symptomatology was observed from D1 to D42 with a mean change of -55.9±23.1mm (P<0.001). This was accompanied by a mean change in OSDI score from baseline of -44.6±15.9 (P<0.001) and a substantial soothing sensation in 82.3% of patients. Clinically significant improvements were observed for all ocular symptoms (mainly burning/irritation, stinging/pain, feeling of ocular dryness, foreign body sensation, itching/pruritus). Conjunctival hyperemia significantly decreased in 96.8% of patients (56.5% displayed no conjunctival hyperemia at D42 versus 0% at baseline). All signs and symptoms improved by D14 and further improved at D42. Investigators assessed the ocular efficacy of T2769 as very satisfactory or satisfactory for 91.9% of patients at D42. T2769 was well tolerated, with no ocular adverse events and only a few ocular symptoms upon instillation. CONCLUSION Management of moderate-to-severe DED patients with the new formulation T2769, combining NAAGA to HA and trehalose, led to rapid and significant improvements in dry eye signs and symptoms with good tolerability.

Background An artificial-tear formulation containing the dual polymers hydroxypropyl guar (HPG) and hyaluronic acid (HA) is approved for the treatment of dry-eye disease (DED). The present study compared the efficacy and safety of the HPG-HA dual-polymer formulation vs a sodium hyaluronate (SH)-containing artificial-tear formulation in patients with DED. Methods In a prospective, 6-week, multicenter, double-masked, parallel-group study, patients with DED aged ≥18 years and total ocular surface staining (TOSS) score ≥4 and ≤9 were randomized (1:1) to receive either HPG-HA or SH four times a day for 42 days. Changes from baseline in TOSS (primary end point), impact of dry eye on everyday life (IDEEL) treatment-satisfaction scores (effectiveness and inconvenience), and tear-film breakup time (TFBUT) at day 42 were assessed using a fixed-sequence testing strategy. Noninferiority was assessed on the primary end point based on the upper limit of two-sided 95% CIs for mean treatment difference (HPG-HA or SH) <2 units. Results In total, 99 patients were randomized (HPG-HA, n= 50; SH, n= 49). At day 42, the least square (LS) mean ± SE change from baseline in TOSS was −1.16±0.24 and −0.92±0.23 in the HPG-HA and SH groups, respectively, and the treatment difference was −0.24±0.33 (95% CI −0.90 to 0.42). Noninfe-riority was demonstrated as the upper limit of the 95% CI was <2 units. LS mean change from baseline at day 42 for HPG-HA vs SH was −3.18 (P=0.4817) in IDEEL treatment-effectiveness scores, −12.56 (P=0.0001) in treatment-inconvenience scores, and 0.30 seconds (P=0.5789) in TFBUT. Conclusion The HPG-HA dual-polymer formulation was noninferior to the SH lubricant eye-drops for improvement in ocular surface staining in DED. HPG-HA did not show improvement over SH in IDEEL treatment-satisfaction scores. No new safety findings were reported.

No abstract available

This study evaluated the effectiveness of hyaluronic acid and trehalose (HA/trehalose) eyedrops in managing dry eye disease (DED) symptoms by measuring tear stability and administering a DED questionnaire. Sixty patients were treated with either HA/trehalose eyedrops (Tear A) or carmellose sodium eyedrops (Tear B) as controls. The tear breakup time (TBUT) and non-invasive breakup time (NIBUT) were monitored, and patients completed the standard patient evaluation of eye dryness (SPEED) questionnaire. After two months of twice-daily applications, patients treated with the HA/trehalose eyedrops demonstrated significant improvements in the NIBUT (12.98 ± 3.22 s) and TBUT (12.95 ± 2.98 s), indicating increased tear stability. Moreover, they reported lower dry eye sensation (6.70 ± 4.94 SPEED score points), suggesting a reduction in DED symptoms. These findings underscore the efficacy of HA/trehalose eyedrops in improving both the objective and subjective signs of DED, with twice-daily application enhancing ocular surface conditions and reducing patient-reported symptoms.

BACKGROUND AND OBJECTIVES Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and hyaluronic acid (HA) in women aged 42-54 years (mixed-hormonal status) versus ≥ 55 years (postmenopausal) and with moderate and severe DED. METHODS This was a post-hoc analysis of three clinical trials assessing the efficacy of artificial tears containing trehalose (3%) and HA (0.15%) in women with an Ocular Surface Disease Index (OSDI) ≥ 18. Patients instilled one drop of the artificial tears in each eye 3 to 6 times daily and were evaluated at baseline and after 84 ± 7 days for DED symptom severity (OSDI), hyperemia (McMonnies scale), tear break-up time (TBUT), corneal and conjunctival staining (Oxford and Van Bjisterveld scales), tear production (Schirmer I test), and ocular symptoms. RESULTS A total of 273 women were evaluated, 61 of age 42-54 years; 212 of ≥ 55 years. DED symptoms, as measured by the OSDI, decreased significantly with the treatment in both age groups (p < 0.0001). Conjunctival hyperemia decreased significantly and TBUT increased significantly in both groups, especially in women of age 42-54 (both p < 0.0001). The global (corneal and conjunctival) staining score decreased significantly in both groups, but also more in women of age 42-54 years. No differences were observed between age groups for any of the variables measured, except for visual acuity. DED symptoms were consistently reported more frequently by the mixed hormonal status women, but also the effect of the treatment was more pronounced in this group. CONCLUSIONS Artificial tears with trehalose and HA significantly improved the symptoms of DED in women aged 42-54 and ≥ 55 years. The decrease in symptoms was more pronounced in women of age 42-54 years, suggesting better mechanisms of recovery from inflammation and loss of ocular surface homeostasis.

The aim of this study is to report the clinical outcomes of oral supplementation with curcumin-phospholipid in addition to hyaluronic acid-based tear substitute for the management of dry eye disease (DED). Patients with a diagnosis of DED confirmed by pathological values of both NIKBUT <10 s. and OSDI Questionnaire score > 12 were included. Patients were randomized to receive 2 different treatments: 0.25% hyaluronic acid-based tear substitute 3 time daily (Group 1) or as above plus curcumin-phosphatidylcholine complex tablets once a day (Group 2). Patients were evaluated at baseline (T0) and after 90 days of treatment (T1) by means of Keratograph for the measurement of NIKBUT, TMH, meibomian gland dropout and bulbar redness. Overall, data from 90 eyes of 45 patients were included. Group 1 consisted of 48 eyes of 24 patients, while group 2 included 42 eyes of 21 patients. When comparing median values of both groups at T0, no statistically significant differences were found for all parameters; instead for T1, statistically significant differences were found for redness and OSDI compared to Group 1. In group 1, a statistically significant reduction after the treatment was detected for Nikbut average and OSDI questionnaire; while in group 2, a statistically significant reduction after treatment was recorded for Nikbut average, bulbar redness and OSDI questionnaire. The addition of an oral supplement containing curcumin-phospholipid may help in a greater improvement of bulbar redness and subjective ocular symptoms compared to the treatment with tear substitutes alone for the management of DED.

The purpose of this prospective study was to evaluate the efficacy of the perioperative use of a hyaluronic acid (HA) and trehalose ophthalmic solution (Thealoz® Duo) in reducing post-cataract surgery dry eye signs and symptoms in patients with mild/moderate dry eye disease (DED). One hundred and twenty patients, scheduled for unilateral cataract surgery, were randomized into three groups: (1) group A: HA/trehalose three times/day in the preoperative week and for 5 postoperative weeks; (2) group B: HA/trehalose for only 5 postoperative weeks; (3) group C: no artificial tears. In groups A and B, OSDI (Ocular Surface Disease Index) questionnaire scores were significantly lower than group C at all the postoperative visits; in group A they were significantly lower than group B on the day of surgery, with similar results in the first and fifth weeks after surgery. In groups A and B, break-up time (BUT) was significantly higher than group C during the postoperative period (p ≤ 0.001). In comparison to the preoperative values, BUT in group A remained stable 7 days after surgery; however, in groups B and C, it significantly decreased. In conclusion, the HA/trehalose ophthalmic solution effectively reduced post-cataract surgery DED signs and symptoms in patients with mild/moderate DED, particularly if also administered in the preoperative period.

Purpose To evaluate the effects of a hydroxypropyl guar (HPG) and hyaluronic acid (HA) ophthalmic solution in terms of post-cataract surgery dry-eye disease (DED) prevention. Patients and Methods In this retrospective study, the data of 419 patients not previously affected by DED, who had undergone unilateral cataract surgery in 17 Italian centers with different perioperative lubricating regimens, were retrospectively reviewed. Patients who had instilled HPG/HA solution 3 times/day in the preoperative week and for two postoperative months were included in group A; group B only instilled HPG/HA for two postoperative months; group C did not instill any perioperative artificial tears. All patients followed the same antibiotic and anti-inflammatory postoperative topical regimen. The scores of SPEED (Standard Patient Evaluation of Eye Dryness) questionnaire, tear break-up time (BUT) and corneal fluorescein staining (CFS, Oxford scale), performed at the preoperative visit and at one, four and eight postoperative weeks, were evaluated. Results In groups A and B, the SPEED scores were significantly lower than group C in the whole postoperative period. In group A, the SPEED scores were significantly lower than group B 1 and 4 weeks after surgery (p<0.001 and p=0.021). In group C, 25% of patients reported symptom scores corresponding to mild-moderate dry eye 4 and 8 weeks after surgery. The fluorescein tear BUT in groups A and B was significantly higher than group C in the whole postoperative period (p<0.001). In group A, BUT was significantly higher than group B 4 weeks after surgery (p=0.016). More patients showed no corneal fluorescein staining (CFS grade=0) in groups A and B than group C at all the postoperative visits. Conclusion The hydroxypropyl guar and hyaluronic acid ophthalmic solution was effective at reducing post-cataract surgery ocular discomfort and tear instability, particularly if also administered in the preoperative period.

Background Eye drops containing 0.1% hyaluronic acid (HA) and 0.5% carboxymethylcellulose (CMC) applied one drop three times a day per affected eye were compared in patients with moderate keratitis or keratoconjunctivitis related to dry eye disease (DED). Patients and methods This was a prospective, randomized, multicenter, Phase IIIB noninferiority study, with a single-masked phase in parallel mode with two groups over 84 days. The primary efficacy outcome was change in ocular surface (OS) staining between day 0 (D0) and day 35 (D35). The conjunctiva and cornea were stained with lissamine green and fluorescein. Secondary efficacy measures at day 84 (D84) were OS-staining score (SS), ocular comfort index, tear-film breakup time and how patients and investigators rated treatment efficacy and safety. Results At D35, 0.1% HA achieved a 46.6% reduction in OS-SS (−2.03±1.35 points, n=39 patients) and 0.5% CMC treatment, followed by a 34.9% reduction (−1.61±1.69 points, n=38 patients) compared to D0. At D84, the SS difference to D0 improved by −2.58±1.45 points (−59.2%) for 0.1% HA and −2.59±2.27 points (−54.4%) for 0.5% CMC. Ocular comfort-index scores improved, with significantly lower (better) values for stinging and itching on D84 for 0.1% HA. Patients assessed treatment with 0.1% HA as significantly better than 0.5% CMC (Likert scale, 4.82 vs 3.97; P=0.018). Four adverse events (AEs) occurred in four of 41 patients (9.8%) treated with 0.1% HA, and three AEs in two of 39 patients (5.1%) treated with 0.5% CMC. No serious AEs were noted. Conclusion DED signs and symptoms of DED significantly improved with both eye drops. OS staining improved >54% at D84. Treatment was well tolerated, with only minor AEs <10%. 0.1% HA and 0.5% CMC were equally safe and effective. Significant and nonsignificant results were constantly in favor of 0.1% HA.

Purpose To evaluate the clinical efficacy of oral hyaluronic acid (HA) in patients with dry eye disease (DED). Study Design Prospective randomized controlled trial. Methods This trial enrolled 54 subjects and they were randomized into the study or control group. The inclusion criteria were as follows: (1) >18 years of age; (2) distance best-corrected visual acuity ≥ 20/40 Snellen equivalent in each eye; (3) IOP ≤ 21 mmHg in both eyes; (4) ocular surface disease index (OSDI) score of ≥18 and <65; (5) <10 seconds of tear break up time (TBUT); (6) >5 corneal spots of corneal fluorescein staining (CFS); and (7) ≤ 10 mm/5 min of the Schirmer test. All subjects were treated with a topical HA, and the study group was supplemented with oral HA. OSDI, TBUT, CFS, and the Schirmer test were evaluated for ocular surface parameters. Results 24 patients were assigned in the study group. Significant improvement of OSDI, TBUT, and CFS was observed at 1 month and 3 months after oral HA administration in the study group. At baseline and follow-up at 1 and 3 months, OSDI scores were 61.8 ± 16.2, 47.3 ± 11.6, and 42.3 ± 9.1, respectively (P < 0.001). TBUT was improved after treatment for 1 month and 3 months (4.2 ± 1.1; P=0.005 and 4.7 ± 1.1; P < 0.012). There were also statistically significant improvements in the CSF (1.8 ± 1.0, 0.8 ± 0.7; P < 0.001) at baseline compared with those at 1 month. Conclusions A combined supplement of both oral and topical HA more efficiently improves corneal epithelial wound healing and related symptoms than topical HA alone, in DED.

Purpose This randomized, observer-masked, crossover study investigated the effect of two hyaluronic acid/trehalose-based containing formulations, with different physical properties, on the signs and symptoms in patients with moderate to severe dry eye disease (DED). Methods In one group, patients received a mixture of sodium hyaluronate and trehalose (HT, Thealoz Duo®) for use during the day. In the other group, patients received a more viscous formulation consisting of hyaluronic acid, trehalose, and carbomer (HTC-gel, Thealoz Duo Gel) to use pro re nata. Both groups used HTC-gel before going to bed. Clinical standard tests for DED were performed at the beginning and end of each one-week period. Further, patient satisfaction including quality of sleep was assessed using a visual analogue scale. Results Corneal fluorescein and conjunctival lissamine green staining scores decreased, and tear breakup time (BUT) increased for both groups (p < 0.001 each). Mean instillation frequency was 3.1 ± 2.6 drops/day when using HT and 1.9 ± 2.2 drops/day when using HTC-gel (p=0.02). A significant improvement in the quality of sleep was observed with both treatments (p=0.01). Conclusions Our results show improvement in signs and symptoms of DED in both groups. While instillation of HTC-gel resulted in a lower instillation frequency, both formulations of trehalose showed good clinical efficacy. This trial is registered with NCT02980913.

The aim of this work was to assess the tolerability, safety, and efficacy of an ophthalmic topical formulation containing helenalin from Arnica montana and hyaluronic acid 0.4% (HA) in patients with mild-to-moderate Dry Eye Disease (DED) exhibiting positive Matrix Metalloproteinase 9 (MMP-9) test results. Tolerability and safety were evaluated in 24 healthy subjects. Participants were instructed to apply one drop of the formulation three times a day in the study eye, for 2 weeks, followed by a clinical follow-up of 21 days. Efficacy was studied in 48 DED patients randomized into Study (Group 1/receiving the studied formulation) or Control (Group 2/Receiving HA 0.4% eye lubricant) groups for 1 month. Assessments included an MMP-9 positivity test, conjunctival impression cytology (CIC), Ocular Surface Disease Index (OSDI), non-invasive film tear breakup time (NIBUT), non-invasive average breakup time (NIAvg-BUT), ocular surface staining, Schirmer’s test, and meibomiography. A crossover design with an additional 1-month follow-up was applied to both groups. Healthy subjects receiving the studied formulation exhibited good tolerability and no adverse events. Regarding the efficacy study, Group 1 exhibited a statistically significant reduction in the MMP-9 positivity rate compared to Group 2 (p < 0.001). Both Group 1 and Group 2 exhibited substantial improvements in OSDI and NIBUT scores (p < 0.001). However, Group 1 demonstrated a significant improvement in NI-Avg-BUT and Schirmer’s test scores (p < 0.001), whereas Group 2 did not (p > 0.05). Finally, after the crossover, the proportion of MMP-9-positive subjects in Group 1 increased from 25% to 91.6%, while Group 2 showed a significant decrease from 87.5% to 20.8%. Overall, the topical formulation containing sesquiterpene helenalin from Arnica montana and hyaluronic acid was well tolerated and exhibited a favorable safety profile. Our formulation reduces DED symptomatology and modulates the ocular surface inflammatory process; this is evidenced by the enhancement of CIC, the improvement of DED-related tear film status, and the reduction of the MMP-9 positivity rate.

Background: To assess the clinical efficacy, tolerability and safety of a new-generation ophthalmic solution containing cross-linked hyaluronic acid 0.15% trehalose 3%, liposomes 1% and sterylamine 0.25% (Trimix® Off Health Italia, Firenze, Italy) (CXHAL) versus trehalose 3% (Thealoz®, Thea Pharmaceuticals, Clermont-Ferrand, France) (TRS) in subjects with moderate to severe dry eye disease (DED). Patients and methods: In this prospective, observational cohort study, 41 subjects with moderate to severe dry eye were enrolled and divided into two age- and sex-matched groups. Group 1 was treated with CXHA eye drops, and group 2 was treated with TRS eye drops four times daily for 2 months. All subjects were evaluated at baseline (V0) and at day 60 ± 3 (V1). The examination comprised Best Corrected Visual Acuity (BCVA) and Symptom Assessment in Dry Eye (SANDE). Tear osmolarity was evaluated using the TearLab Osmolarity System®; Keratograph 5M (Oculus, Wetzlar, Germany) was performed to assess tear meniscus height (TMH), fluorescein tear break-up time (TBUT) and corneal and conjunctival fluorescein staining and meibography; furthermore, slit lamp evaluation was performed for eyelid erythema and edema, conjunctival chemosis and hyperemia and Meibomian gland secretion quality. Results: All patients completed the treatment. BCVA remained stable in both groups, and no adverse events were reported. After 2 months, both groups showed statistically significant improvements for SANDE (p = 0.001 and p = 0.012, respectively), TBUT values (p < 0.001 and p < 0.001, respectively) and staining (p = 0.004 and p = 0.001, respectively) as compared to baseline values. Group 1 showed a statistically significant improvement in SANDE frequency and tear osmolarity (p = 0.02 and p = 0.001, respectively), whereas chemosis was significantly reduced in group 2. The amount of TBUT improvement was statistically higher in group 1 compared to that in group 2 (p = 0.041). Conclusion: A new-generation multiple-action ophthalmic solution was safe and clinically effective in the treatment of moderate and severe dry eye, with significant improvements in the main ocular surface parameters.

Background/aims To investigate the clinical outcomes and antimicrobial activity of an hypochlorous acid hygiene solution compared with hyaluronic acid wipes for blepharitis treatment in patients with dry eye disease (DED). Methods This study involved 48 eyes of 48 patients affected by blepharitis with mild to moderate DED. 24 patients were treated with a hypochlorous acid hygiene solution (HOCL group) and 24 patients were treated with hyaluronic acid wipes (HYAL group) for a period of 4 weeks. The following clinical outcomes were assessed before (V0) and after the treatment period (V1): non-invasive keratograph break up time (NIK-BUT), tear film BUT (TF-BUT) tear meniscus height (TMH), Keratograph meibography, Meibomian Gland Yield Secretion Score (MGYSS), Corneal Staining Score (CSS), Schirmer test I, Keratograph conjunctival redness score and Ocular Surface Disease Index (OSDI). Moreover, microbiological analysis of upper and lower eyelid margins was performed at V0 both before and 5 min after treatment. Results After 1-month NIK-BUT and TF-BUT significantly increased in HOCL group, while they did not show a statistically significant difference in HYAL group compared with baseline. OSDI, TMH and MGYSS showed a significant difference in both groups, while Schirmer test, meibography, CSS and conjunctival redness score did not significantly change in both groups. Bacterial load showed a significant reduction in both groups, more pronounced in HOCL group compared with HYAL group. Conclusions Hypochlorous acid hygiene solution can be securely employed in blepharitis treatment considering the satisfying clinical outcomes and antimicrobial activity compared with hyaluronic acid wipes.

Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). In this study, we aimed to compare the effects of eyelid warming treatment using either TheraPearl Eye Mask (Bausch & Lomb Inc., New York, USA) or Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) in a Norwegian population with mild to moderate MGD-related DED. An open label, randomized comparative trial with seventy patients (49 females, 21 males; mean age 53.6 years). Patients were randomly assigned to treatment with Blephasteam (n = 37) or TheraPearl (n = 33). All received a hyaluronic acid based artificial tear substitute (Hylo-Comod, Ursapharm, Saarbrücken, Germany). Patients were examined at baseline, and at three and six months initiation of treatment. Treatment efficacy was primarily evaluated by fluorescein breakup time (FBUT) and Ocular Surface Disease Index (OSDI) scores. Other outcome measures included ocular surface staining (OSS), Schirmer’s test, and meibomian quality and expressibility. Baseline parameter values did not differ between the groups. After six months of treatment, Blephasteam improved FBUT by 3.9 s (p < 0.01) and OSDI by 13.7 (p < 0.01), TheraPearl improved FBUT by 2.6 s (p < 0.01) and OSDI by 12.6 (p < 0.01). No difference between treatments was detected at 6 months (p = 0.11 for FBUT and p = 0.71 for OSDI), nor were there differences in the other tested parameters between the treatment groups. Blephasteam and TheraPearl are equally effective in treating mild to moderate MGD in a Norwegian population after 6-months of treatment. Clinicaltrials.gov ID: NCT03318874; Protocol ID: 2014/1983; First registration: 24/10/2017.

Introduction Dry eye disease (DED) is a prevalent condition, particularly among IT workers with prolonged screen exposure, leading to symptoms like dryness and visual fatigue due to reduced blinking and tear film instability. Preservative-free artificial tears are increasingly recommended for their safety and efficacy in managing DED. Aim This study evaluates the efficacy of preservative-free artificial tears containing 0.15 –0.4% hyaluronic acid, administered twice daily, in improving DED symptoms in IT professionals. Secondary aims include assessing changes in tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), and Schirmer test scores. Materials and Methods This prospective, non-randomized study included 83 IT workers (46 men, 37 women; mean age 28.4 ± 4.7 years) with DED symptoms, working over 8 hours daily on computers. Participants used preservative-free artificial tears (0.15–0.4% hyaluronic acid) twice daily for one month. Clinical assessments (TBUT, OSDI, Schirmer test) were conducted at baseline and after 30 days. Statistical analysis used paired t-tests (p < 0.05). Results Of 83 participants, 79 completed the study. The OSDI scores decreased, from 25.6 ± 8.2 to 14.3 ± 5.1 (p < 0.001), indicating symptom improvement. TBUT increased, from 7.8 ± 2.1 to 11.5 ± 1.9 seconds (p < 0.001), showing enhanced tear film stability. The Schirmer scores slightly improved, from 12.4 ± 4.3 mm to 14.1 ± 3.8 mm (p = 0.04). No adverse effects were reported. Conclusion Preservative-free artificial tears significantly improve DED symptoms and tear film stability in IT workers, supporting their use as a safe, effective treatment. Further studies with control groups are warranted.

Background/Objectives: Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by tear film instability, hyperosmolarity, inflammation, and oxidative stress. First-line treatment for DED relies on lubricating and hydrating eye drops, usually containing hyaluronic acid (HA), which supports tear film stability and epithelial healing. However, HA alone cannot correct oxidative stress, a key driver of cellular damage and inflammation in DED. Accordingly, this study aimed to evaluate the antioxidant capacity of Malva sylvestris tincture (MalvaT) and its physicochemical properties in experimental eye-drop formulations containing HA. Methods: The antioxidant activity of reconstituted MalvaT lyophilisate (Malva) was assessed in cell-free assays against several oxygen radicals and in cell-based assays using the human HaCat keratinocyte cell line. The refractive index was measured in eye-drop formulations containing 0.15% or 0.3% HA and 0.5% MalvaT. Surface tension was assessed in eye-drop formulations containing 0.15% HA and increasing concentrations (0.25-2.0%) of MalvaT. Results: Malva showed potent oxygen radical scavenging activity in both cell-free and cell-based assays, indicating its antioxidant capacity and the efficient cellular uptake of antioxidant components. The refractive indices of experimental eye-drop solutions containing HA and MalvaT were close to that of tear fluid (1.334). The surface tension of the experimental eye-drop formulations, while not impacted by 0.15% HA, was significantly reduced by increasing concentrations of MalvaT (p < 0.0001). At the concentration of 0.5% MalvaT, the mean surface tension was reduced from 68.17 mN/m (HA control) to 59.80 mN/m (HA + MalvaT), thereby bringing it closer to that of tear fluid. Conclusions: This pre-clinical study suggests that combining the antioxidant properties of Malva tincture with the lubricating and hydrating effects of HA in eye-drop formulations exhibiting optimal rheological characteristics may offer a promising therapeutic approach for managing DED.

This study aimed to evaluate the therapeutic efficacy and ocular safety of a multi-wavelength (680 nm, 780 nm, 830 nm) LED irradiation device in a rat model of meibomian gland dysfunction (MGD)-induced dry eye disease (DED). A total of 34 male SD rats were randomly assigned to eight experimental groups, including a normal control group, an MGD induction group, and various treatment groups (LED irradiation, hyaluronic acid, cyclosporine, thermal therapy, and combination therapy). MGD was induced by CFA injection. LED irradiation was administered daily from day 8 to day 22. The clinical ocular assessments included the following: tear break-up time (TBUT), eyelid swelling score, fluorescein corneal staining (FCS), and eyelid telangiectasia. Immunohistochemistry (IHC) analyses of IL-1β, IL-6, and TNF-α were conducted in the cornea, conjunctiva, meibomian glands, and retina. To assess retinal safety, a TUNEL staining procedure was performed. The LED and combination treatment groups showed significant enhancements in TBUT and reductions in FCS, eyelid swelling, and telangiectasia scores in comparison to the MGD group (p < 0.05). In-depth analysis of the data sets revealed a significant decrease in the expression of inflammatory cytokines among the treatment groups. Notably, the expression of IL-1β and IL-6 was significantly reduced in both the LED and combination groups.

PURPOSE: Autologous serum eye drops are considered safe and efficient for the treatment of various ocular surface disorders, including dry eye diseases (DED) caused by the primary and secondary Sjogren syndrome (SS). However, the serum components in patients of SS may be different from those of normal patients and can thus lead to unpredictable therapeutic effects. This study divided the SS patients into active and inactive types based on the erythrocyte sedimentation rate and the presence or absence of active rheumatoid arthritis. METHODS: We compared the serum components of these two groups with standard and multiplex enzyme linked immunosorbent assay arrays and predicted the therapeutic effects of topical autologous serum for the treatment of DED with ocular surface disease index (OSDI) and Oxford Schema scale (OSS). RESULTS: Hyaluronic acid and transforming growth factor b1 levels were significantly higher in the active SS group compared to the inactive SS group (P < 0.01), whereas epidermal growth factors, insulin growth factor 1, and fibroblast growth factor b had no significant differences between these two groups. Active SS group had significantly higher expressions of interleukin (IL) 1 beta, IL 6, and tumor necrosis factor alpha compared to inactive SS patients (P < 0.05). There were no statistical differences in therapeutic effects between these two groups, as measured with the OSDI or OSS. CONCLUSION: Dividing the Sjogren dry eye patients into active and inactive groups may appear as a reasonable method to predict the quality of autologous serum eye drops, but there seems to be no significant predictability to the therapeutic effects.

Clinical studies suggested that Carboxymethyl cellulose (CMC) and Hyaluronic acid (HA) were equally effective in treating DED, other studies have shown that one treatment option outperforms the other.So, this study aimed to explore expert opinions on the use of artificial tear formulations for the effective treatment of dry eye disease (DED) in Indian settings, specifically focusing on prescribing practices for different severity levels of DED. The cross-sectional, questionnaire-based study in which data was collected through a multiple-response questionnaire. The questionnaire comprised 22 questions, covering various aspects such as the clinical characteristics of DED patients and the utilization of artificial tear formulations at different stages of the disease. Among the 54 respondents, 63% of them observed a higher prevalence of DED in individuals aged 25 to 40 years. Furthermore, 77.77% of respondents identified burning or stinging in the eyes as a significant symptom of aqueous deficiency in DED patients. As a first-line treatment for mild DED, 51.85% of participants recommended 0.5% Carboxymethyl cellulose (CMC) eye drops, while 44.44% suggested using combination eye drops containing polyethylene glycol and Propylene glycol (PEG-PG) for moderate DED cases. In the case of severe DED, the majority (68.52%) of respondents preferred prescribing sodium Hyaluronate (SH) eye drops.Experts have recommended the use of CMC eye drops to provide temporary relief from itchiness and pain caused by eye dryness, wind exposure or sun exposure. They have recommended the prescription of 0.5% CMC eye drops three times daily for mild DED patients.

The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign danger signals (including desiccating stress) on the ocular surface with an initial non-specific innate inflammatory response. If unchecked, this can lead to activation of dendritic cells that present antigen and prime T and B cells resulting in an adaptive immune reaction. These reactions generally resolve, but dysfunctional, hyper-responsive immune cells found in systemic autoimmune diseases that are recruited to the ocular surface can amplify inflammatory stress responses in the ocular surface and glandular tissues and result in autoimmune reactions that disrupt tear stability and lead to chronic dry eye disease. We here propose that unique features of the ocular surface immune system and the impact of systemic immune dysregulation in autoimmune diseases, can predispose to development of dry eye disease, and exacerbate severity of existing dry eye.

Keratoconjunctivitis sicca (KCS) is an ocular condition characterized by insufficient tear production and inflammatory irritation, with Sjögren's syndrome (SS) being a major causative factor. This study aimed to extract patient transcriptomic data from the GEO database to identify signature genes associated with the diagnosis and treatment of KCS and the expression of three key genes were experimentally verified. We performed a difference analysis on the SS patient dataset and performed a Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the resulting genes. Additionally, a Weighted Gene Co-expression Network Analysis (WGCNA) was constructed. Machine learning techniques were employed to analyze the most strongly correlated gene modules with SS traits. These findings were further validated using KCS immune-correlation microarrays as a validation set. The correlation of the three identified genes with 22 immune cells was assessed through immune infiltration analysis. Subsequently, a rat model of desiccated keratoconjunctivitis was established, and the modeling situation and expression of characteristic genes were analyzed at the morphological, tissue, and molecular levels. Bioinformatic prediction revealed that the expression of JAK1, SKI, ZBTB16 not only differed in the machine learning validation set, but also correlated with some immune cells in the immune infiltration analysis. The results of animal experiments showed that the transcription and expression levels of these three genes were significantly different in rat KCS tissues and normal tissues, and there were also differences in the expression of JAK1 and SKI in rat peripheral blood, as well as significant up-regulation of the expression of related inflammatory factors in KCS tissues. Through bioinformatics prediction and animal experimental validation, this study identified three differentially expressed genes in SS mediated KCS patients, which provide new potential biological targets for the diagnosis and treatment of KCS.

The aim was to compare the outcomes acquired from the OSA-Vet® device with conventional quantitative and qualitative tear tests and between groups within each test, in brachycephalic dogs both healthy and those diagnosed with keratoconjunctivitis sicca. The dogs were divided into four groups: healthy dogs (HD), with mild KCS (MIKCS); moderate KCS (MOKCS); severe KCS (SKCS). All patients underwent ocular surface diagnostic examination in the following order, with a 10-minute interval between tests: non-invasive tear film breakup time (TBUTNI - OSA-Vet®), tear meniscus height (TMH-OSA-Vet®), meniscometry (I-Tear® test), Schirmer Tear Test-1 (STT-1), and tear film breakup time (TBUT). Kruskal-Wallis H tests were performed to establish the difference between the groups and Spearman´s correlation coefficient test to assess the correlation between tests. And an analysis of variance (ANOVA) followed by Tukey-Kramer post-hoc test was performed for TMH. Results with (p <.05) were considered statistically significant. The correlation of conventional tests in relation to those obtained by OSA-Vet® proved to be low, except between TBUTNI (OSA-Vet®) and TBUT in MOKCS, with a strong correlation (r =.925). In the comparison between TBUTNI (OSA-Vet®) and TBUT in MIKCS the correlation was moderate (r =.547) as well as STT-1 and I-Tear® test in MOKCS (r =.416). In the comparison between groups, the main result observed was a significant difference between all the KCS groups and HD, in the TBUT and TBUTNI (OSA-Vet®) test. The OSA-Vet® and conventional tests are useful for evaluating the ocular surface of brachycephalic dogs. However, the OSA-Vet® does not correlate well with conventional standardized tests.

Purpose The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls. Methods Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire in dry eye (SANDE) scores were collected for all patients. Results Two hundred fifty-three of the 507 tear proteins analyzed were significantly different in patients with SS compared to controls. Two hundred forty-one if the proteins were upregulated and 12 were downregulated. One hundred eighty-one differentially expressed proteins were significantly correlated with all four clinical parameters: TBUT, CF staining, CJ staining, and SANDE score. Conclusions These findings indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip. The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls. The upregulated tear proteins correlated with clinical measures of dry eye symptoms and disease severity. Translational Relevance Tear proteins could serve as important biomarkers for studying pathogenesis and in clinical diagnosis and management of SS KCS.

Sjögren syndrome (SS) is an autoimmune condition that targets the salivary and lacrimal glands, with cardinal clinical signs of dry eye (keratoconjunctivitis sicca, KCS) and dry mouth. The conjunctiva of SS patients is often infiltrated by immune cells that participate in the induction and maintenance of local inflammation. The purpose of this study was to investigate immune-related molecular pathways activated in the conjunctiva of SS patients. Female SS patients (n=7) and controls (n=19) completed a series of oral, ocular surface exams. Symptom severity scores were evaluated using validated questionnaires (OSDI and SANDE). All patients fulfilled the ACR/EULAR criteria for SS and the criteria for KCS. Fluorescein and lissamine green dye staining evaluated tear-break-up time (TBUT), corneal and conjunctival disease, respectively. Impression cytology of the temporal bulbar conjunctiva was performed to collect cells lysed and subjected to gene expression analysis using the NanoString Immunology Panel. 53/594 differentially expressed genes (DEGs) were observed between SS and healthy controls; 49 DEGs were upregulated, and 4 were downregulated (TRAF5, TGFBI, KLRAP1, and CMKLRI). The top 10 DEGs in descending order were BST2, IFITM1, LAMP3, CXCL1, IL19, CFB, LY96, MX1, IL4R, CDKN1A. Twenty pathways had a global significance score greater or equal to 2. Spearman correlations showed that 29/49 upregulated DEGs correlated with either TBUT (inverse) or OSDI or conjunctival staining score (positive correlations). Venn diagrams identified that 26/29 DEGs correlated with TBUT, 5/26 DEGs correlated with OSDI, and 16/26 correlated with conjunctival staining scores. Five upregulated DEGs (CFB, CFI, IL1R1, IL2RG, IL4R) were uniquely negatively correlated with TBUT. These data indicate that the conjunctiva of SS patients exhibits a phenotype of immune activation, although some genes could be inhibitory. Some of the DEGs and pathways overlap with previous DEGs in salivary gland biopsies, but new DEGs were identified, and some of these correlated with symptoms and signs of dry eye. Our results indicate that gene analysis of conjunctiva imprints is a powerful tool to understand the pathogenesis of SS and develop new therapeutic targets.

OBJECTIVES To estimate the frequency and breed-related risk factors for keratoconjunctivitis sicca (KCS) in dogs under UK primary veterinary care. METHODS Analysis of cohort electronic patient record data through the VetCompass Programme. Risk factor analysis used multivariable logistic regression. RESULTS There were 1456 KCS cases overall from 363,898 dogs [prevalence 0.40%, 95% confidence interval (CI) 0.38-0.42] and 430 incident cases during 2013 (1-year incidence risk 0.12%, 95% CI 0.11-0.13). Compared with crossbreds, breeds with the highest odds ratio (aOR) for KCS included American cocker spaniel (aOR 52.33: 95% CI 30.65-89.37), English bulldog (aOR 37.95: 95% CI 26.54-54.28), pug (aOR 22.09: 95% CI 15.15-32.2) and Lhasa apso (aOR 21.58: 95% CI 16.29-28.57). Conversely, Labrador retrievers (aOR 0.23: 95% CI 0.1-0.52) and border collie (aOR 0.30: 95% CI 0.11-0.82) had reduced odds. Brachycephalic dogs had 3.63 (95% CI 3.24-4.07) times odds compared to mesocephalics. Spaniels had 3.03 (95% CI 2.69-3.40) times odds compared to non-spaniels. Dogs weighing at or above the mean bodyweight for breed/sex had 1.25 (95% CI 1.12-1.39) times odds compared to body weights below. Advancing age was strongly associated with increased odds. CLINICAL SIGNIFICANCE Quantitative tear tests are recommended within yearly health examinations for breeds with evidence of predisposition to KCS and might also be considered in the future within eye testing for breeding in predisposed breeds. Breed predisposition to KCS suggests that breeding strategies could aim to reduce extremes of facial conformation.

OBJECTIVE To establish tear film osmolarity (TFO) values in Pugs and Shih-Tzus, with and without keratoconjunctivitis sicca (KCS). ANIMALS STUDIED A total of 82 adult dogs were evaluated. PROCEDURE The inclusion criteria for the healthy group was a Schirmer tear test (STT-1) ≥15 mm/min with no clinical signs of KCS, whereas those with KCS had clinical signs and a STT-1 ≤10 mm/min. All animals underwent complete ophthalmological evaluation prior to STT-1 and TFO. Student's t tests were used to compare STT-1 and TFO in KCS and healthy eyes as well as possible differences in TFO between breeds. In addition, a linear regression to model the relationship between the two variables (STT-1 and TFO) was performed. A P-value ≤ 0.05 was considered statistically significant. RESULTS STT-1 results were significantly lower (p = 0.0001) in the KCS group (4.46 ± 1.74) compared with the control group (18.80 ± 2.02). Mean TFO results were significantly higher in the KCS group (353.02 ± 16.58 mOsm/L) (p < 0.0001) compared with the control group (315.27 ± 6.15 mOsm/L). The formula Y = 365.059-2.625 * X significantly predicts (p < 0.001) the value of the variable Y (TFO mOsm/L) as a function of the variable X (STT-1 mm/min), with a coefficient of determination of 0.71. CONCLUSIONS The results revealed differences in TFO and STT-1 between KCS and healthy dogs. Additionally, STT-1 and TFO values were correlated with the aim to use STT-1 values to predict TFO values in brachycephalic breeds.

The lacrimal functional unit (LFU) regulates tear production, composition, distribution and clearance to maintain a stable protective tear layer that is essential for maintaining corneal epithelial health. Dysfunction of the LFU, commonly referred to as dry eye, leads to increases tear osmolarity and levels of inflammatory mediators in tears that cause ocular surface epithelial disease, termed keratoconjunctivitis sicca (KCS). Corneal changes in KCS include glycocalyx loss, barrier disruption, surface irregularity inflammatory cytokine/chemokine production, cornification and apoptosis. These can reduce visual function and the increased shear force on the corneal epithelium can stimulate nociceptors sensitized by inflammation causing irritation and pain that may precede frank clinical signs. Therapy of keratoconjunctivitis sicca should be tailored to improve tear stability, normalize tear composition, improve barrier function and minimize shear forces and damaging inflammation to improve corneal epithelial health.

Purpose: To evaluate the ocular signs and tests for keratoconjunctivitis sicca (KCS) in the absence of a gold standard. Methods: Cross-sectional study of participants from the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry. Participants had oral/ocular/rheumatologic examinations, blood/ saliva samples collected, and salivary gland biopsy. Latent class analysis (LCA) identified clusters of patients based on 3 to 4 predictor variables relating to signs or tests of KCS. The resulting model-based “gold standard” classification formed the basis for estimated sensitivity and specificity associated with these predictors. Results: A total of 3514 participants were enrolled into SICCA, with 52.9% classified as SS. LCA revealed a best-fit model with 2 groups. For the gold standard–positive group, an abnormal tear breakup time, ocular staining score (OSS), and Schirmer I had a sensitivity of 99.5%, 91.0%, and 47.4%, respectively. For the gold standard–negative group, an abnormal tear breakup time, OSS, and Schirmer I had a specificity of 32.0%, 84.0%, and 88.5%, respectively. OSS components (fluorescein and lissamine staining), exhibited a sensitivity of 82.6% and 90.5%, respectively, in the gold standard–positive group, whereas these signs in the gold standard–negative group had a specificity of 88.8% and 73.0%, respectively. Conclusions: OSS and its components (fluorescein and lissamine staining) differentiated 2 groups from each other better than other KCS parameters and had relatively high sensitivity and specificity.

OBJECTIVE To assess the clinical safety and efficacy of adjunctive therapy using Vizoovet to ameliorate clinical signs of keratoconjunctivitis sicca (KCS) in dogs. ANIMALS STUDIED Twenty client-owned dogs. PROCEDURES Canine patients diagnosed with KCS were enrolled in this prospective study. Patients were randomly selected to receive either Vizoovet or GenTeal drops twice daily in addition to twice daily tacrolimus 0.03% solution. Data were collected from only one eye of each patient and included STT-1, IOP, TFBUT, and results of objective clinical scoring performed by pet owners. Statistical significance was set at P ≤ .05. RESULTS In all, 20 dogs (20 eyes) were enrolled in this prospective randomized study. Females (n = 12; 60%) outnumbered males (n = 8; 40%) and all dogs were spayed/neutered. Mean age of all dogs was 10.6 ± 3.79 years. In both treatment groups, the improvement in STT-1 values over the course of the study was significant (P = .002). When comparing the STT-1 improvements between groups, no significance was found (P = .78). In both groups, the improvement in TFBUT was significant (P = .0018). When comparing the TFBUT improvements between groups, no significance was found (P = .14). Squinting, rubbing, ocular discharge, and medication administration scores all significantly improved throughout the course of the study; however, they did not differ significantly between groups. Throughout the study, no adverse side effects were noted clinically or by the pet owner in either group. CONCLUSIONS AND CLINICAL RELEVANCE Adjunctive treatment with Vizoovet was as safe and effective as GenTeal drops at improving clinical signs of dry eye in dogs.

Abstract Objective To investigate meibomian gland (MG) morphology by noncontact infrared meibography in Shih Tzu dogs with or without keratoconjunctivitis sicca (KCS). Procedures Fourteen eyes of 12 Shih Tzu dogs (mean age of 10.7 years, range of 7‐13 years) presented to Yakumo Animal Hospital or Triangle Animal Eye Clinic from 2011 to 2017 with clinical signs and a Schirmer tear test (STT) result consistent with KCS (<10 mm/min) were examined. Twenty‐eight eyes of 16 Shih Tzu dogs (mean age of 12.4 years, range of 8 to 15 years) with a STT > 15 mm/min served as healthy controls. Both groups of dogs underwent routine slitlamp biomicroscopy followed by noncontact infrared meibography of the upper eyelid with both desktop‐type and mobile‐type systems. Results Meibography revealed morphological abnormalities of MGs in 13 eyes of 11 dogs with KCS. The abnormalities included gland shortening in 64% and gland dropout in 64% of the 14 eyes in the KCS group. Morphological changes were also observed in MGs of 16 eyes of 10 dogs in the control group. These changes included shortening in 46% and dropout in 17.8% of the 28 eyes in the control group. Dropout was significantly more common in eyes with KCS than in control eyes (P < 0.01). Conclusions The frequency of MG abnormalities is increased in Shih Tzus with KCS compared with control animals. A reduced quality of the tear film associated with increased evaporation and reduced retention of tear fluid likely exacerbates the effects of a reduced tear volume in animals with aqueous deficiency.

The objective of this study was to assess the performance and reproducibility of the two currently used ocular surface staining scores in the assessment of keratoconjunctivitis sicca in Sjögren syndrome (SS) research classification.

Background The prevalence of keratoconjunctivitis sicca (KCS) associated with Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) (HTLV-1/KCS) has been estimated at around 37%, but its clinical manifestations are poorly described. Purpose To determine the prevalence and associated factors of HTLV-1/KCS in a large cohort of HTLV-1-infected individuals living in Salvador, Brazil. Methods A cross-sectional study was conducted between June 2004 and September 2017 at the Integrative and Multidisciplinary Center for HTLV in Salvador, Bahia-Brazil. Data from 758 HTLV-1-infected patients was collected. A complete ophthalmologic examination was performed in both eyes. Lacrimal function was evaluated by breakup time, Rose Bengal and Schirmer I Tests. KCS diagnosis was considered in the presence of at least two out of three positive tests. HTLV-1 proviral load Crude and Adjusted Prevalence Rates (PR) with 95% Confidence Intervals (95% CI) were estimated using multivariate Poisson Regression with robust error variance. Results The overall prevalence of KCS was 31.7%, with higher rates observed in HTLV-1-associated myelopathy/tropical spastic paraparesis patients (crude PR: 1.84; CI95%: 1.50–2.26) even after adjusting for age, sex, time of HTLV-1 diagnosis and schooling (adjusted PR: 1.63; CI95%: 1.31–2.02). Proviral load, low corrected visual acuity, burning and/or pain and itching were all significantly higher in patients with KCS. Conclusion Burning and/or pain and itching and low corrected visual acuity were the most common alterations of HTLV-1/KCS. High Proviral load was found to be associated with the presence of KCS. It is strongly recommended that HTLV-1 patients undergo periodic ophthalmologic examination to promote the early diagnosis of KCS and prevent the consequences associated with dry eye disease.

The aim of this exploratory study was to evaluate the efficacy of a periophthalmic cream of a pool of fatty acids (FAG®) in association with 0.15% hyaluronate eye drops in alleviating the clinical symptoms of keratoconjunctivitis sicca (KCS) in a case series of dogs. The study was conducted on 10 dogs diagnosed with idiopathic KCS. All dogs had been previously treated with topical tobramycin alone, which had been ineffective in improving clinical signs. The affected eyes were treated with 2 applications daily of a periophthalmic cream of FAG® and 1 drop 3 times a day of 0.15% of hyaluronate eye drops for 8 weeks. Schirmer tear test I (STT I) values were recorded and ocular signs (conjunctival hyperemia, ocular discharge, corneal opacity, vascularization and pigmentation, and discomfort level) were collected, scored on a 3-point scale (grade 0, grade 1, and grade 2). Differences between scores and STT data recorded at baseline and at 8 weeks of therapy were statistically analysed. The effect of treatment was pronounced (increase in STT values by more than 4 mm/min, no signs of inflammation) in 8/18 eyes; moderate (increase in STT values of 3-4 mm/min or mild improvement in signs of corneal/conjunctival inflammation) in 3/18 eyes; and unsatisfactory in 7 of 18 eyes. Median of STT values significantly improved compared with baseline levels, while statistically significant decreases in clinical-sign scores of conjunctival hyperemia, ocular discharge, and discomfort were recorded. However, in moderate and advanced stages, reduction of neovascularization or corneal pigmentation was not observed throughout the treatment period. No noticeable adverse reactions were recorded. Preliminary results indicate that the application of periocular FAG and topical 0.15% hyaluronate eye drops may be a suitable treatment for KCS in dogs in selected cases. A larger comparative study is necessary to further confirm these findings.

Objective Determine morphological and morphometric parameters of corneal epithelium in dogs, and determine the cellular alterations that occur in canine keratoconjunctivitis sicca (KCS) using impression cytology. Study animals 60 dogs divided into two groups: dogs with Schirmer tear test (STT) at least 15 mm/minute and absence of ocular disease, and dogs with STT less than 15 mm/minute and clinical signs of KCS. Procedures Impression cytology was used to collect corneal samples. The percentage of eyes with cell changes, the number of such cells and the percentage of cells with structural alterations in each group were determined. The possible correlation between corneal epithelium alterations and decreased tear production was evaluated. Results A significant positive correlation existed between STT and the area of the cytoplasm and nucleus of corneal cells. A significant negative correlation was found between STT and the nucleus/cytoplasm ratio, and the presence of cellular changes. A significant difference existed between the numbers of pyknotic nuclei, being higher among animals with all stages of KCS. Conclusion Corneal impression cytology can be used to assess the corneal epithelium in healthy eyes and eyes with KCS, demonstrating its usefulness as a diagnostic tool especially in mild and early cases.

PURPOSE To evaluate the antioxidative effect of artificial tears in the treatment of keratoconjunctivitis sicca (KCS). MATERIAL AND METHODS The study included 43 patients (60 eyes) with severe KCS: 38 women (50 eyes) and 5 men (10 eyes) aged from 27 to 76 years (in average 52 years). Patients were randomly divided into 2 groups; all patients used therapeutic silicone hydrogel soft contact lens (SCL) and instillations of 0.05% Cyclosporin A (CyA) 2 times a day. Patients of the first group (22 people, 30 eyes) used 0.15% hyaluronic acid. In the second group, patients (21 people, 30 eyes) used a tear substitute with similar surface-active component, but with antioxidant properties. The results of the treatment were evaluated using basic and additional research methods at 1, 3, 6 and 12 months. RESULTS Corneal epithelialization was achieved after 1 month of conservative treatment in all patients who wore SCLs and were treated with instillations of 0.05% CyA and artificial tears. Then the lenses were removed and the patients were switched to instillations of CyA and artificial tears. Comparative analysis of the results showed that higher functional indicators were achieved in the second group, where patients used Artelac Rebalance drops with antioxidant properties. CONCLUSION Improvement of clinical and functional parameters in the treatment of severe forms of KCS was achieved by direct action on both links of pathogenesis with minimal amounts of the drugs and the frequency of their use. Subsequent supportive therapy contributed to stabilization of the results and further increase of the functional parameters.

Keratoconjunctivitis sicca (KCS) is a relatively common condition affecting dogs worldwide.1-3 KCS is characterised by a deficiency in the production of the aqueous portion of the tear film, leading to conjunctival hyperaemia, bacterial overgrowth, ocular discharge, corneal vascularisation, corneal pigmentation, ocular pain and loss of vision.4-6 The primary cause of KCS is immune-mediated, but many other causes have also been reported, including congenital, metabolic, infectious, drug-induced, neurogenic, radiation, iatrogenic and idiopathic.7 The diagnosis of KCS is based on the presence of consistent clinical signs and measurement of decreased aqueous tear production using the Schirmer tear test (STT).8 It is largely accepted that an STT value greater than 15 mm/minute is considered normal for dogs, 11 to 14 mm/minute indicates subclinical KCS, 6 to 10 mm/minute indicates mild KCS and 5 mm/minute or less indicates severe KCS. However, several authors have criticised the STT’s variable sensitivity and reproducibility for diagnosing mild KCS.9,10 Due to the variability of STT measurements, a definitive diagnosis for mild cases of KCS may be difficult with the STT alone. As such, there is currently much interest in alternative measures for the diagnosis of KCS. A small number of previous studies …

This study investigated the relationship between clinical severity and percentage of conjunctival antigen-presenting cells (APCs) in Sjögren’s syndrome (SS)-associated keratoconjunctivitis sicca (KCS). KCS clinical severity was based on symptom severity, tear volume, tear break-up time, and ocular surface dye staining. Conjunctival goblet cell density (GCD) was measured in periodic acid Schiff (PAS)-stained membranes. Conjunctival cells obtained by impression cytology were used for flow cytometry to measure percentages of CD45+HLA-DR+ APCs and mature CD11c+CD86+ dendritic cells (DCs). Compared to normal conjunctiva, the percentages of HLA-DR+ and CD11c+CD86+ cells were higher in the conjunctiva of the KCS group (p < 0.05). The percentage of CD45+HLA-DR+ cells positively correlated with clinical severity (r = 0.71, p < 0.05) and negatively correlated with GCD (r = −0.61, p < 0.05). Clinical severity also negatively correlated with GCD (r = −0.54, p < 0.05). These findings indicate that a higher percentage of APCs and mature DCs in the conjunctiva is associated with more severe KCS in SS. These APCs may contribute to the generation of the pathogenic Th1 cells that cause goblet cell loss in KCS.

Objective: In this study, the production of various composite films were formulated using Poly Vinyl Alcohol (PVA) incorporated with multiple polysaccharides containing Acetazolamide (ACZ) by solvent casting method. Methods: Characterization of these ACZ-loaded gel-forming composite films and their complex with biocompatible polymer PVA have been done by advanced characterizing techniques such as weight uniformity, surface pH, thickness, gelling time, gelling capacity, percentage hemolysis, transparency, mechanical properties, Fourier Transform Infrared (FTIR) spectroscopy, impedance analysis, In vitro drug release, ex vivo drug permeation, and ocular irritation assessments. Results: The resulting composite films have appeared transparent and colorless. An FTIR result shows no significant interactions between the polymers. The stress relaxation study established that the addition of polysaccharides enhanced the PVA films' properties while shrinking their elastic properties. However, the residual elastic energy (P0) of the polysaccharide-enhanced films was notably higher than the initial elastic energy (F0). As per the study of stress relaxation, F2 formulation shows the fastest relaxation time. Hemolysis percentages across all films were found to be between 0.114-0.434%, indicating excellent biocompatibility. In the Light transmission study through ultra violet range, F2 formulation shows the highest percentage with 87.43% transmittance. The ocular tissue was not irritated by the synthesized composite film, as confirmed by the Draize eye irritation test. In this study, Ex vivo trans-corneal permeation studies for ACZ exhibited a non-Fickian diffusion design, except formulation F4. The ACZ-loaded gel-forming composite films represent a potential means of treating common eye diseases. Conclusion: Based on these findings, the PVA/polysaccharide composite films appear to be promising candidates for ocular applications.

The major complications associated with the administration of ocular dosage forms are the precorneal loss due to the nasolacrimal drainage and high turnover of tear fluid. In situ forming gels are developed to overcome these complications. In situ gelling systems are polymeric solutions converted into a viscoelastic gel in the ocular surface due to a change in temperature, ionic strength, and pH. Recently, the use of responsive polysaccharides containing in situ gel formulation has increased due to its biocompatible nature, non-toxicity, and biodegradability. The research on in situ gel using polysaccharide in the delivery of drug molecules through the ocular route has diversified in various fields. However, there is no report are available that summaries this progress. The aim of this article is to bridge that lacuna. We discuss different polysaccharides based in situ gel including pH, temperature, ion and multiple sensitive used in ocular drug delivery. The nanoformulation incorporated polysaccharide in situ gels for ocular drug delivery has also been highlighted.

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Ocular drug delivery is one of the most challenging issues in ophthalmology because of the complex physiological structure of the eye. Polysaccharide-based nanomaterials have been extensively investigated in recent years as ideal carriers for enhancing the bioavailability of drugs in the ocular system because of their biocompatibility and drug solubilization. From this perspective, we discuss the structural instability of polysaccharides and its impact on the synthesis process; examine the potential for developing bioactive polysaccharide-based ocular drug nanocarriers; propose four strategies for designing novel drug delivery nanomaterials; and suggest reviewing the behavior of nanomaterials in ocular tissues.

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Widely used polysaccharide-based films in ophthalmic drug delivery have major limitations of inadequate mechanical strength, poor electrical conductivity, and insufficient ocular drug permeability. Moxifloxacin (MFX) biocomposite film of adequate mechanoelectrical properties was developed for sustained ophthalmic drug delivery. Nanocellulose (NC) incorporated (2.5, 5.0, 7.5, and 10.0 %) PVA-tamarind gum-based moxifloxacin composite was prepared using solvent casting method. The addition of NC improved the mechanical properties of the film, demonstrating its ability to strengthen the structure. Stress relaxation (SR) of the film has been augmented (64.67±7.55 to 73.15±0.34 %) due to increased content of NC (0 to 10 %) respectively. Film containing 5 % NC showed the critical edge of tensile strength (11.9±0.39 MPa), and also the threshold limit of electrical conductivity (4.5*107 Ω). The same film exhibited continued drug release as well as erosion-controlled sustained ocular permeation (pH 7.4) and revealed the highest antibacterial activity (ZOI of disc diffusion, cm) with Pseudomonas aeruginosa (4.63±0.15) and Staphylococcus aureus (4.30±0.26) of MFX (≈224 μg). Notably, incorporating NC produced non-irritating and safe for corneal delivery as confirmed by the Draize model test. Our findings suggested that the NC-containing PVA-tamarind gum-based composite film holds a promising approach for sustained ophthalmic delivery of MFX.

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Light-activated liposomes permit site and time-specific drug delivery to ocular and systemic targets. We combined a light activation technology based on indocyanine green with a hyaluronic acid (HA) coating by synthesizing HA–lipid conjugates. HA is an endogenous vitreal polysaccharide and a potential targeting moiety to cluster of differentiation 44 (CD44)-expressing cells. Light-activated drug release from 100 nm HA-coated liposomes was functional in buffer, plasma, and vitreous samples. The HA-coating improved stability in plasma compared to polyethylene glycol (PEG)-coated liposomes. Liposomal protein coronas on HA- and PEG-coated liposomes after dynamic exposure to undiluted human plasma and porcine vitreous samples were hydrophilic and negatively charged, thicker in plasma (~5 nm hard, ~10 nm soft coronas) than in vitreous (~2 nm hard, ~3 nm soft coronas) samples. Their compositions were dependent on liposome formulation and surface charge in plasma but not in vitreous samples. Compared to the PEG coating, the HA-coated liposomes bound more proteins in vitreous samples and enriched proteins related to collagen interactions, possibly explaining their slightly reduced vitreal mobility. The properties of the most abundant proteins did not correlate with liposome size or charge, but included proteins with surfactant and immune system functions in plasma and vitreous samples. The HA-coated light-activated liposomes are a functional and promising alternative for intravenous and ocular drug delivery.

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To assess efficacy and safety of laughter exercise in patients with symptomatic dry eye disease. Non-inferiority randomised controlled trial. Recruitment was from clinics and community and the trial took place at Zhongshan Ophthalmic Center, Sun Yat-sen University, the largest ophthalmic centre in China, between 18 June 2020 to 8 January 2021. People with symptomatic dry eye disease aged 18-45 years with ocular surface disease index scores ranging from 18 to 80 and tear film break-up time of eight seconds or less. Participants were randomised 1:1 to receive laughter exercise or artificial tears (0.1% sodium hyaluronic acid eyedrop, control group) four times daily for eight weeks. The laughter exercise group viewed an instructional video and participants were requested to vocalise the phrases "Hee hee hee, hah hah hah, cheese cheese cheese, cheek cheek cheek, hah hah hah hah hah hah" 30 times per five minute session. Investigators assessing study outcomes were masked to group assignment but participants were unmasked for practical reasons. The primary outcome was the mean change in the ocular surface disease index (0-100, higher scores indicating worse ocular surface discomfort) from baseline to eight weeks in the per protocol population. The non-inferiority margin was 6 points of this index score. Main secondary outcomes included the proportion of patients with a decrease from baseline in ocular surface disease index score of at least 10 points and changes in dry eye disease signs, for example, non-invasive tear break up time at eight weeks. 299 participants (mean age 28.9 years; 74% female) were randomly assigned to receive laughter exercise (n=149) or 0.1% sodium hyaluronic acid (n=150). 283 (95%) completed the trial. The mean change in ocular surface disease index score at eight weeks was -10.5 points (95% confidence interval (CI) -13.1 to -7.82) in the laughter exercise group and -8.83 (-11.7 to -6.02) in the control group. The upper boundary of the CI for difference in change between groups was lower than the non-inferiority margin (mean difference -1.45 points (95% CI -5.08 to 2.19); P=0.43), supporting non-inferiority. Among secondary outcomes, the laughter exercise was better in improving non-invasive tear break up time (mean difference 2.30 seconds (95% CI 1.30 to 3.30), P<0.001); other secondary outcomes showed no significant difference. No adverse events were noted in either study group. The laughter exercise was non-inferior to 0.1% sodium hyaluronic acid in relieving subjective symptoms in patients with dry eye disease with limited corneal staining over eight weeks intervention. ClinicalTrials.gov NCT04421300.

Dry eye disease (DED), the most prevalent ophthalmological condition worldwide, can cause severe ocular discomfort and even visual impairment. Effective yet safe therapeutics for severe DED are still highly demanded. Herein, considering the important role of excessive reactive oxygen species (ROS) in triggering DED, an eye-drop nano-formulation of catalase (CAT) self-assembled with cysteine-modified chitosan (CS-Cys) is designed for DED treatment. Upon eye-drop administration of CS-Cys/CAT nanoparticles, CS-Cys can form disulfide bonds with abundant thiols in the mucin layer of the tear film, anchoring catalase to the corneal surface. Thus the excess ROS accumulated on the ocular surface can be effectively eliminated, resulting in a regulated tear microenvironment. In mouse and rabbit models, it is verified that CS-Cys/CAT eye drops can offer excellent therapeutic effects, especially in promoting the recovery of damaged epithelium and increasing tear secretion. Remarkably, CS-Cys/CAT eye drops showed notably better therapeutic performance than clinically used cyclosporin and dexamethasone, as well as several new DED drugs in clinical trials. Thus, the work presents a unique nanoparticulate eye-drop-based ocular delivery system to allow prolonged ocular retention of protein therapeutics, and such nanoformulation formulated by fully biocompatible/biodegradable components possesses significant translational potential for effective and safe DED treatment.

Artificial tears remain the cornerstone for managing dry eye disease. The current study's real-world efficacy test of carboxymethylcellulose (CMC), polyethylene glycol (PEG) 400, or sodium hyaluronate (SH)-based lubricants highlights their similar effects on noninvasive tear film parameters over the short term. However, patients reported better relief with SH-based lubricants. This study aimed to compare the short-term impact of different artificial tear formulations on tear film in moderate dry eye disease patients. A prospective, double-masked, controlled study randomly allocated moderate dry eye disease patients into five groups of artificial tears: 0.5% CMC, 1% CMC, 0.1% SH-trehalose, 0.4% PEG 400-0.3% propylene glycol (PG), and 0.1% SH-0.4% PEG 400-0.3% PG. Noninvasive tear breakup time (NIBUT), tear meniscus height, and bulbar redness (Keratograph 5M; OCULUS Optikgeräte, Wetzlar, Germany) were assessed (in a controlled environment chamber 68 to 70°F; 35% relative humidity) at baseline and every 15 minutes for 1 hour after a drop instillation in the left eye. The right eye was an internal control. At 1 hour, subjects were asked for a change in subjective symptomatology (scales 0 to 4). A linear mixed-effect model was used for analysis. Each artificial tear group had 20 patients (100 patients). All groups had similar dry eye disease types and durations, baseline ocular surface disease index scores, and tear film parameters. All artificial tears showed significant improvement in NIBUT values at all time points from baseline compared with contralateral eyes. The change in NIBUT values was similar between different artificial tears at all time points. Bulbar redness scores and tear meniscus height showed no significant change in either eye with time or artificial tears. All patients reported improvement in dry eye disease symptomatology, with significant differences observed between 1% CMC and SH-PEG-PG (p=0.01), 0.5% CMC and SH-PEG-PG (p<0.0001), and 0.5% CMC and 0.1% SH-trehalose (p=0.01), where SH-based tear drops performed better. Tear film stability improves following a single drop of CMC, SH, and PEG-based artificial tears, although these artificial tears do not differ in their short-term effect.

Hyaluronic acid is a widely available, biocompatible, polysaccharide with distinguishing physiochemical properties which inspire its application throughout several fields of medicine. We aim to investigate the application of hyaluronic acid and its effectiveness throughout several fields of medicine, including several therapies administered and prescribed by general health practitioners. We conducted a systematic review on randomized controlled trials about the physiochemical properties of hyaluronic acid and its application through primary care. Studies included in this review were peer reviewed and met our inclusion criteria. Factors were clustered into the following: uses throughout several fields of medicine, physiochemical properties, bioavailability, tolerance, effectiveness, and adverse effects. Therapies with hyaluronic acid provided long-lasting, pain relieving, moisturizing, lubricating, and dermal filling effect. Tissue hydration, elasticity, and durability improved. Adjunct therapy with hyaluronic acid provides longer-lasting therapeutic effect when compared to the use of glucocorticosteroids and NSAIDs in osteoarthritic chronic diseases, is well-established in ophthalmology due to its lubricating properties for the corneal endothelium, and improves tissue hydration and cellular resistance to mechanical damage in aesthetic dermatology, and has marginal adverse effects. Several trials indicated its role in tumor markers, liver diseases, and in pharmaceuticals, but further research would be necessary to draw conclusive results in those fields.

Trehalose, a disaccharide of glucose, is a naturally occurring nontoxic and nonreducing bioactive sugar. Trehalose is synthetized by many organisms when cells are exposed to stressful conditions, including dehydration, heat, oxidation, hypoxia or even anoxia. Although trehalose is not synthesized by mammalian cells, it has recently been demonstrated to have a number of important properties that indicate its utility in humans. Trehalose enables wound healing by protecting cells, especially cell membranes, from oxidative injury and dessication. When the injured cornea is treated with trehalose, corneal inflammation, scar formation and corneal neovascularization are suppressed. In dry eye disease, trehalose decreased cell apoptosis and reduced oxidative, inflammatory and proteolytic activity at the ocular surface. In UVB irradiated cornea, trehalose suppressed photodamage evoked by UVB rays. It decreased the intracorneal inflammation and reduced corneal neovascularization. Trehalose prevented postoperative fibrous scar formation after ocular surgery, such as glaucoma filtration surgery. The non-toxicity of trehalose allows its administration in humans for extended periods and enables its use in various disease states.

Dry eye is the most prominent pathology among those involving the ocular surface: a decrease of the aqueous (less frequent) or the lipid (more frequent) component of the tear film is the cause of the diminished stability of tears that is observed in this pathology. Dry eye shows a clear distribution linked to both sex (being more frequent among women) and age (increasing with aging). Therefore, specific treatments taking into account the etiology of the disease would be desired. The role of lactoferrin and its functional mimetic lactobionic acid are reported here as a possible remedy for age-related dry eye.

Dry eye disease (DED), a prevalent ocular disorder, affects nearly half the global population, bringing enormous health and economic burden. Currently, the predominant treatments for DED involve the administration of artificial tears, which is often hindered by continuous administration and constant reactive oxygen species (ROS) stimulus. Therefore, hyaluronan (HA)-modified cerium oxide (CeO

Dry eye disease (DED) is characterized by chronic inflammation and an unstable tear film. Stem cells have shown potential for DED treatment, but the main challenge lies in improving cell delivery effectiveness. Here, we developed eye drops for autoimmune DED treatment using porous arginine-glycine-aspartic acid (RGD)-modified alginate microcarriers with mesenchymal stem/stromal cells (MSCs) (RGD-Alg@MSCs). These microcarriers provided a favorable microenvironment for large-scale cell expansion while maintaining stemness with ideal mechanical properties for ocular application. In vitro, RGD-Alg@MSCs demonstrated significantly enhanced therapeutic effects compared to conventional MSCs, including improved cell viability, reduced apoptosis and reactive oxygen species, and enhanced release of immunomodulatory factors. Transcriptomic analysis revealed distinct molecular mechanisms underlying these enhanced therapeutic effects. In the mouse model, RGD-Alg@MSCs exhibited prolonged ocular retention and enhanced tear production, promoted corneal healing, and suppressed inflammation by inhibiting dendritic cell activation and T

Dry eye is a medical problem of epidemic proportions, especially among the elderly in developed countries. The treatment of dry eye is still largely inadequate because there is no way of permanently restoring normal tear function and secretion at present. At present, virtually all therapeutic regimens include tear supplements; however, their main drawbacks are the need for frequent instillation, inadequate ocular surface protection and limited mode of action, focusing on rewetting only. A new gellable lubricant eye drop (Systane lubricant eye drops, Alcon) has been designed using the novel concept of a pH-sensitive hydroxypropyl-guar component that prevents surface desiccation, reduces friction and acts as a mucomimetic. The purpose of this review is to consider this topical therapy and its properties. Currently published data on Systane is reviewed, putting an accent on its novel multiple modality of action. By being pH sensitive, Systane adapts its viscosity to the ocular surface pH, which tends to be higher in dry eye. It becomes more viscous when the eye is drier, thus, providing better ocular surface protection. In addition, its characteristics reduce ocular surface friction, which is another factor that exacerbates dry eye symptoms. Data published so far show that it is also well tolerated by the patient, thus, significantly reducing dry eye symptoms and improving the patient's quality of life. By implementing this novel approach, Systane has contributed significantly to dry eye treatment.

Trehalose is a natural disaccharide synthesized in various life forms, but not found in vertebrates. An increasing body of evidence demonstrates exceptional bioprotective characteristics of trehalose. This review discusses the scientific findings on potential functions of trehalose in oxidative stress, protein clearance, and inflammation, with an emphasis on animal models and clinical trials in ophthalmology. The main objective is to help understand the beneficial effects of trehalose in clinical trials and practice, especially in patients suffering from ocular surface disease. The discussion is supplemented with an overview of patents for the use of trehalose in dry eye and with prospects for the 2020s.

One in four patients attending ophthalmic clinics report symptoms of dry eye, making it one of the most common complaints seen by ophthalmologists. Aqueous-layer deficiency is the most common form of dry eye and is frequently caused by decreased secretion of tears by the lacrimal glands. Evaporative dry eye is often secondary to meibomian gland disease and results in a defective lipid layer. Tear replacement or preservation using artificial tears and/or punctal occlusion are the mainstay of treatment. Newer forms of therapy were designed to modify the underlying disease process. These include the use of topical cyclosporin A, autologous serum, and sodium hyaluronate drops, which suppress underlying inflammation, provide growth factors, and prevent the onset of squamous metaplasia in ocular surface epithelium. Hormonal therapy might have a role in the future of dry eye therapy.

To compare the clinical efficacy and safety of acupuncture and sodium hyaluronate eye drop in the treatment of aqueous deficiency dry eye. A total of 60 patients (120 eyes) with aqueous deficiency dry eye were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 1 case dropped out). In the control group, sodium hyaluronate eye drop were used, one drop at a time, 4 times a day, for 14 consecutive days. In the observation group, acupuncture was applied at bilateral Shangjingming (Extra), Cuanzhu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5), and Tongziliao (GB 1) , once a day, treatment for 6 days with the interval of 1 day was required, for 14 consecutive days. The tear meniscus height (TMH), Schirmer Ⅰ test (SⅠT), ocular surface disease index (OSDI) score, non-invasive tear break-up time (NIBUT), and corneal fluorescein sodium staining (FLS) score were compared between the two groups before and after treatment, and the safety of the treatment of the two groups was observed. Compared with those before treatment, after treatment, TMH, SⅠT and NIBUT were increased ( Acupuncture and sodium hyaluronate eye drop can both effectively treat aqueous deficiency dry eye, acupuncture has obvious advantages in improving TMH and basic tear secretion, and reducing the subjective symptoms of patients. Acupuncture for dry eye is safe.

This study aimed to assess the effectiveness and safety of intense pulsed light (IPL) therapy plus topical 0.05% cyclosporine A (CsA) eye drops to treat Sjögren's Syndrome-related dry eyes (SS-DE). In this prospective, randomized trial included, 60 individuals with SS-DE symptoms were randomized to receive topical eye drops containing either 0.1% sodium hyaluronate (Group S) or 0.05% CsA (Group C) plus IPL therapy. Before the first treatment (baseline), and at 12, 16, and 20 weeks after treatment commencement, we assessed the best corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI) score, the Schirmer I test (SIT), noninvasive tear breakup time (NBUT), corneal fluorescein staining (CFS), meibomian gland (MG) dropout, lid margin abnormality, MG expressibility, and meibum quality. Both groups showed significant improvements in the OSDI, NBUT, CFS, MG expressibility, and meibum quality (all Treatment with 0.05% CsA eyedrops plus IPL therapy could significantly reduce the issues and physical discomfort of patients with SS-DE. Registered on 20 July 2021, with the registration number ChiCTR2100049059.

Dry eye syndrome after cataract surgery is a common complication that may affect the patient's visual comfort and quality of life. Because the surgery may affect the secretion and quality of tears in the eye, resulting in dry and uncomfortable eyes.This study aimed to investigate the therapeutic effects of recombinant bovine basic fibroblast growth factor (rb-bFGF) eye drops on dry eye syndrome after cataract surgery and to analyze its impact on tear secretion and corneal injury. This is a retrospective study. A total of 126 patients (126 eyes) with dry eye syndrome after cataract surgery were treated between January 2021 and October 2022. patients were randomly divided into a study group (64 patients, 64 eyes) and a control group (62 patients, 62 eyes). Both groups were treated with sodium hyaluronate eye drops, while the study group received rb-bFGF eye drops for four weeks in addition to the sodium hyaluronate eye drops. The clinical efficacy, results of tear secretion test (SIT), tear film break-up time (BUT), corneal fluorescein staining, corneal topography examination, oxidative stress indicators, ocular surface disease index (OSDI) score, and drug adverse reactions were compared between the two groups. The study group exhibited a significantly higher total effective treatment rate (96.88%) compared to the control group (85.48%), suggesting the enhanced efficacy of rb-bFGF eye drops. Moreover, the study group demonstrated extended tear secretion length and tear film break-up time, indicating improved tear film stability and ocular surface health. Additionally, the study group showed reduced corneal fluorescein staining score and improved corneal surface regularity index, indicative of enhanced corneal integrity and smoothness. Notably, tear superoxide dismutase levels were elevated, while lipid peroxide levels were lowered in the study group, underscoring the potential antioxidative effects of rb-bFGF. The study group also exhibited a lower OSDI score, suggesting reduced ocular discomfort and improved quality of life. Although the study group had a slightly higher incidence of adverse reactions (9.38%) compared to the control group (8.06%), the difference was not statistically significant. Particularly significant is the statistical significance highlighting the heightened total effective treatment rate in the study group, indicating the potential of rb-bFGF eye drops in promoting favorable therapeutic outcomes. rb-bFGF eye drops are safe and effective in treating dry eye syndrome after cataract surgery. They can help regulate tear secretion, repair corneal damage, and improve dry eye symptoms. Despite the retrospective design and relatively small sample size of this study, further randomized controlled trials and larger sample size may be needed to verify the robustness of the results, but this study is important for guiding the treatment strategy and optimizing patient care for dry eye after cataract surgery.

Dry eye disease (DED) is a common ocular surface disorder. Esculin and digitalis possess anti-inflammatory and anti-oxidant properties, which may benefit patients with DED. This study aimed to assess the therapeutic efficacy of esculin and digitalis glycosides (EAD) eye drops, either alone or in combination with 0.3% sodium hyaluronate (SH) eye drops, in treating DED. In this randomized controlled trial, 78 participants with DED (78 eyes) were included and divided into three groups: Group A received 0.3% SH, Group B received EAD, and Group C received 0.3% SH combined with EAD eye drops for 4 weeks. The efficacy of the treatments was assessed at 2 and 4 weeks using the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Schirmer I test (SIt), and corneal fluorescein staining (CFS) as primary evaluation metrics. After 4 weeks of treatment, Group A showed a decrease in OSDI and an increase in SIT (p < 0.05). Group B showed a decrease in OSDI score (P < 0.05) and a significant improvement in SIt (P < 0.01). Group C demonstrated a significant increase in both TBUT and SIt values at the 2-week mark. Improvements were noted across all parameters, including OSDI score, TBUT, SIt, and CFS score after 4 weeks of treatment (P < 0.05). The total effective rate for participants in Group C was 88.46%, significantly higher than Group A's rate of 65.38% (P < 0.05). In conclusion, the combination of EAD eye drops with 0.3% SH eye drops proved more effective than either treatment alone.

Dry eye disease (DED) is a complex and multifactorial ocular surface disease. Reactive oxygen species (ROS) are of pivotal importance in the inflammatory processes and biological dysfunction associated with DED. In this study, an injectable hydrogel, designated as OHACDgel, was created by combining oxidized HA-containing aldehyde groups (OHA) and gelation (gel) via dynamic covalent linkages of the hydrazine bonds, is employed as the carrier, while polyethylene imine-functionalized carbon dots (PEI-CD) can form dynamic chemical bonds with the hydrogel, thus prolonging the retention time of the ocular surface. OHACDgel has been demonstrated to diminish ROS overproduction markedly, reduce the expression of pro-inflammatory factors, inhibit the transformation of macrophages into a pro-inflammatory phenotype, reverse corneal epithelial defects, restore goblet cell function, and enhance tear secretion. Furthermore, the biocompatibility of OHACDgel has been demonstrated, presenting a rapid and straightforward therapeutic option for potential applications in DED.

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Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of

In this study, we aimed to investigate the effect of different hyaluronic acid (HA)-containing artificial tears on dry eye disease (DED) treatment in combination with intense pulsed light (IPL) therapy. A retrospective cohort study was conducted, and the participants received IPL therapy and HA-containing artificial tears. There were 42 and 40 eyes in the 0.10% and 0.15% HA groups after selection, respectively. The main outcomes were the postoperative non-invasive tear break-up time (NITBUT), Schirmer II test results, ocular surface stain, and numbers of DED-related symptoms. A generalized linear model was utilized to produce the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the main outcomes between groups. At the three-month follow-up, the NITBUT was significantly higher in the 0.15% HA group (

Frequent topical administration of hypotensive eye drops in glaucoma patients may lead to the development of dry eye disease (DED) symptoms, because of tear film destabilization and the adverse effects associated with antiglaucoma formulations. To address all this, in the current study preservative-free latanoprost-loaded (0.005 % w/v) synthetic phosphatidylcholine (1,2-dioleoyl-sn-glycero-3-phosphocholine 0.75 % w/v, 1,2-dimyristoyl-sn-glycero-3-phosphocholine 0.25 % w/v) liposomes dispersed in the mucoadhesive polymer hyaluronic acid (0.2 % w/v), containing the osmoprotective ingredients betaine (0.40 % w/v) and leucine (0.90 % w/v) (LAT-HA-LIP), have been prepared and further characterised. Permeation and retention evaluations on a validated ex vivo porcine eye model revealed that the active metabolite latanoprost acid was quantified only starting from LAT-HA-LIP once passing conjunctiva, sclera and choroid compared to the marketed latanoprost (0.005 % w/v) benchmark (MF). The liposomal formulation outperformed MF when applied to the corneal tissue. Additionally, distribution and interactions within corneal and scleral tissues were investigated by means of two-photon microscopy with liposomal formulations containing coumarin-6. Furthermore, acute and chronic tolerance studies on rabbits revealed no signs of discomfort or ocular damage. Schirmer's test, tear osmolarity, tear breakup time (TBUT) and fluorescence staining evaluated through the Oxford grading scale, were assessed as DED diagnostic parameters over a 25-day monitoring period; LAT-HA-LIP consistently maintained levels comparable to physiological solution (0.9 % w/v NaCl) used as control, with a slight increase of TBUT values from day 15 (6.00 ± 0.63 s for control, 7.00 ± 0.78 s for LAT-HA-LIP at day 15, p = 0.0066). A daily topical application of LAT-HA-LIP for 15 consecutive days, effectively lowered IOP in a sustained way (2.51-3.88 mmHg mean IOP reduction over the 5-15-day period). These results highlight the clinical relevance of the proposed technological platform, able to provide IOP reduction during the simulated long-term administration and simultaneous ocular surface protection with potential for the treatment of glaucoma.

Dry eye disease (DED) is a multifactorial condition caused by tear deficiency and accompanied by ocular surface damage. Recent data support a key role of oxidative and inflammatory processes in the pathogenesis of DED. Hyaluronic acid (HA) is widely used in artificial tears to treat DED by improving ocular hydration and reducing surface friction. Crocin (Cr), the main constituent of saffron, is a renowned compound that exhibits potent antioxidant and anti-inflammatory effects. The present study was undertaken to assess the viscosity and muco-adhesiveness of a photoactivated formulation with crosslinked HA (cHA), Cr, and liposomes (cHA-Cr-L). Our aim was also to evaluate whether cHA-Cr-L may exert cytoprotective effects against oxidative and inflammatory processes in human corneal epithelial cells (HCECs). Viscosity was measured using a rotational rheometer, and then the muco-adhesiveness was evaluated. Under hyperosmolarity (450 mOsm), the HCECs were treated with cHA-Cr-L. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of reactive oxygen species (ROS) were measured using the DCF assay. The combined action of cHA-Cr-L produced a higher viscosity and muco-adhesiveness compared to the control. The anti-inflammatory effect of cHA-Cr-L was achieved through a significant reduction of IL-1β and TNFα (

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The dry eye disease (DED) is a common disease and a frequent reason for consultation at community pharmacy. DED has a high impact on patients' quality of life (QoL); therefore, an appropriate treatment should aim to improve it. Artificial tears constitute the cornerstone for DED management and the main treatment recommended by pharmaceutical indication. To study the effect of eyedrops based on hyaluronic acid, Centella asiatica and Aloe vera on the QoL of patients with DED. In parallel, treatment adherence, tolerance and safety of the product were evaluated. Post-authorization, open, prospective and multicentric clinical study. Patients received the treatment for 60 days. To study the effect on QoL, patients completed the OSDI© questionnaire before starting the treatment, and at 30 and 60 days of treatment. Treatment adherence was assessed by means of units' reconciliation and the safety, through adverse events monitoring. la enfermedad de ojo seco (EOS) es una patología común y un motivo de consulta frecuente en farmacia comunitaria. Esta tiene un gran impacto en la calidad de vida (QoL) de los pacientes; por ello, un tratamiento adecuado debería mejorarla. Las lágrimas artificiales constituyen la base para el manejo de la EOS y el principal tratamiento de indicación farmacéutica. Estudiar el efecto de unas gotas oculares a base de ácido hialurónico, Centella asiática y Aloe vera en la QoL de pacientes con EOS. Paralelamente, la adherencia al tratamiento, la tolerancia y seguridad del producto, fueron evaluados. Estudio clínico posautorización, abierto, prospectivo y multicéntrico. Los pacientes recibieron el tratamiento durante 60 días. Para estudiar el efecto sobre la QoL, los pacientes cumplimentaron el cuestionario OSDI© antes de iniciar el tratamiento y a los 30 y 60 días de tratamiento. La adherencia se evaluó mediante la reconciliación de los envases y la seguridad mediante un seguimiento de los eventos adversos. Los pacientes tratados con las gotas oculares, población por intención de tratar (ITT, n=44), obtuvieron mejoras clínicamente importantes en la QoL, sintomatología y función visual, pues la puntuación OSDI© disminuyó de 32,80 (DE=23,00) (basal, EOS severo) a 12.64 (DE=15,32) (estado normal, p<0,001), y a 9.22 (DE=10,37) (estado normal, p<0,001), a los 30 y 60 días, respectivamente. Más del 70 % de los pacientes se adhirieron al tratamiento. El perfil de seguridad fue favorable. Se observaron 4 efectos adversos oculares de intensidad leve. No se plantearon problemas de seguridad. Las gotas oculares objeto de estudio podrían ser una opción de tratamiento efectiva y segura para mejorar la QoL de pacientes con EOS.

Dry eye is a substantial problem in a large number of human and canine patients. Numerous laboratory models for tear deficiency exist using genetically predisposed rodent models, animals treated with topical anti-muscarinics, or those kept in environments with increased air flow to produce the ocular surface changes seen in human patients. Canine keratoconjunctivitis sicca, seen in many thousands of dogs kept as companion animals, can provide a valuable spontaneous model for testing tear replacement medications that might better model disease in human patients, existing as it does in an outbred population that live in the same environments as their owners. Here the development of a crosslinked hyaluronic acid topical drop is described together with the results of trials on dogs with spontaneous keratoconjunctivitis sicca. Although hyaluronic acid in its native form in tear replacement drops shows a Newtonian rheology, the crosslinked product described here behaves in a non-Newtonian manner, with the same shear thinning shown by the tear film itself. The crosslinked product thus shows itself as a potentially valuable tear replacement medication for the human dry eye population as well as for dogs with the same condition.

To examine the effects of topical 3-isobutyl-1-methylxanthine treatment on tear-film osmolarity, conjunctival goblet-cell densities, and corneal epithelial glycogen levels in a rabbit model for keratoconjunctivitis sicca. Keratoconjunctivitis sicca was surgically induced in the right eyes of 16 rabbits. In a masked protocol, eight of these operated-on eyes underwent treatment for 12 weeks with a 3.0-mmol solution of 3-isobutyl-1-methylxanthine. The remaining eight operated-on eyes were left untreated and served as controls. The 3-isobutyl-1-methylxanthine treatment resulted in a rapid and significant decrease in tear osmolarity and sodium (P < .5) and potassium levels (P < .05) and a significant increase in conjunctival goblet-cell densities and corneal epithelial glycogen levels compared with untreated and operated-on controls (P < .001). 3-Isobutyl-1-methylxanthine rapidly and significantly decreased tear-film osmolarity in this rabbit model for keratoconjunctivitis sicca and restored conjunctival goblet-cell densities and corneal glycogen levels, thus reversing the disease process.

A double-blind cross-over comparative study on the effect of Lacrisert versus oculoguttae viscosae and saline has been conducted. Lacrisert is a soluble solid tear substitute which is applied once-a-day. The object was to compare the safety and patient acceptability of Lacrisert and oculoguttae viscosae, and to compare the efficacy of Lacrisert to oculoguttae viscosae and saline. Twenty-nine patients suffering from primary Sjögren's syndrome (Copenhagen criteria), 2 male and 27 female, age: median 56 years, range 32-79 years. Lacrisert was applied once-a-day, and saccharose crystals of similar appearance was used as placebo. All patients were treated for 4 periods of 3 weeks: Lacrisert + saline versus placebo + saline and Lacrisert + oculoguttae viscosae versus placebo + oculoguttae viscosae. The patients were examined before entering the study and after each of the 4 periods using: slit-lamp, corneal sensitivity, BUT, Schirmer-1-test and Rose-bengal staining. Comparing Lacrisert to saline a significant improvement in BUT (p less than 0.01) and in Rose-bengal staining (p less than 0.01) was found, whereas other patients were unchanged. Comparing Lacrisert with oculoguttae viscosae no significant difference in clinical parameters could be detected. The patients complained of minor discomfort. Most prominent was a tendency to loose the Lacrisert due to an inadequate solubilisation of the rod caused by the lack of aqueous tears. We conclude that Lacrisert may help patients with primary Sjögren's syndrome provided that they have some secretory capacity left in the tear glands.

To present ophthalmic findings, clinical data, and treatment outcomes of 16 juvenile Yorkshire Terriers with severe unilateral keratoconjunctivitis sicca. Each of the 16 dogs exhibited extreme unilateral dryness associated with blepharospasm, mucoid discharge, and corneal vascularization. Ages of affected dogs at presentation ranged from 5 months to 4 years. Mean Schirmer tear test (STT) result for affected eyes was 1 mm/min. Topical application of 0.2% cyclosporine to the affected eye was not associated with improvement in STT values in any dog. Clinical signs subjectively improved with topical application of 20% chondroitin sulfate ophthalmic solution in some dogs, and transposition of the parotid duct was performed in three dogs. Histopathologic examination in one dog failed to show evidence of orbital lacrimal gland tissue. Clinical signs, age of presentation, disease severity, and lack of response to treatment are consistent with breed-related unilateral aplasia or hypoplasia of the lacrimal gland. Lacrimal gland aplasia or hypoplasia should be considered in young dogs with severe unilateral ocular dryness, especially female Yorkshire Terriers.

In order to evaluate the therapeutic value of an unpreserved carboxymethylcellulose-based artificial tear in treatment of keratoconjunctivitis sicca (KCS), 56 patients with severe keratoconjunctivitis sicca were enrolled, at a single study center, in a randomized, double-masked, 8-week comparison with a preserved hydroxypropylmethylcellulose (HMC)-based artificial tear. Patients treated with the carboxymethylcellulose (CMC)-based tear showed significant improvement in fluorescein staining, symptoms, and impression cytology grades. Patients treated with HMC-based tears showed minimal improvement in a few variables. Impression cytology specimens were analyzed by a modified technique that maps the distribution of the various grades present on the specimen. With this technique, improvement in the cytology grades was noted in the group of patients using CMC-based tears. The improvement correlated with observed decreases in symptoms of discomfort and with scores for superficial punctate staining. This study supports the observed therapeutic value of unpreserved CMC-based artificial tears and suggests the possible reversal of squamous metaplasia in patients with KCS. Further studies are required to separate the benefit of the CMC formulation from the benefits of preservative elimination.

The effect of sodium hyaluronate eye drops in the treatment of severe keratoconjunctivitis sicca (KCS) was evaluated in a double masked crossover trial, comparing the effect of a 0.1% solution, a 0.2% solution and placebo in 20 patients. We found significantly decreased rose bengal staining and increased break-up time following 0.2% treatment compared to placebo. No significant difference was found in the Schirmer values and the cornea sensitivity. The patients significantly preferred sodium hyaluronate treatment. We conclude that sodium hyaluronate eye drops seem to be a valuable new agent in the management of KCS.

We have continued our study of the tear film and ocular surface in our full KCS (keratoconjunctivitis sicca) rabbit model up to 52 weeks post-operatively. Tear film osmolarity remains elevated, conjunctival goblet cell density remains decreased, and the conjunctival epithelium remains abnormal. Corneal epithelial glycogen levels decreased progressively, and at 44 weeks post-operatively rabbits developed abnormal rose Bengal staining of the affected cornea that was shown to be associated with morphologic abnormalities at 52 weeks. Rabbits began rubbing the affected eye after the development of corneal staining. Our full KCS rabbit model demonstrates the features of the human disease.

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We developed and tested ocular inserts containing epidermal growth factor (EGF) for a causal treatment of keratoconjunctivitis sicca (KCS). The inserts, consisting of different alginates with hydroxyethylcellulose (HEC) as a lubricant and release modifier, released EGF over time periods ranging from a few hours up to several days. The stability of EGF was high, having a protein half-life of approximately 548 days. A clinical pilot study suggests an amelioration of both the main symptoms and the objective criteria: tear film break-up (BUT) time and lissamine green score. Our results show that EGF treatment of KCS is highly promising.

Ten women with primary Sjögren's syndrome were treated with sodium pentosan polysulfate (Elmiron) 150 mg X 2 daily for 4 months in an open investigation. No subjective or objective improvement was recorded.

An unpreserved artificial tear substitute containing 0.1% sodium hyaluronate was compared with a preparation containing 1.4% polyvinyl alcohol and 0.5% chlorobutanol in a controlled, double-masked, randomized study in patients with moderately severe keratoconjunctivitis sicca. Patients were evaluated initially, at 1, 4, and 8 weeks. The dry-eye status was evaluated by means of tear-film osmolality, tear breakup time, rose bengal staining, Schirmer's test (without anesthesia), and ocular surface-impression cytology. In general, neither preparation was found to be superior to the other. In both study groups, the mean tear-film osmolality and rose bengal staining score improved over the eight-week study, but the degree of squamous metaplasia of the bulbar conjunctival surface, as shown by impression cytology, did not change significantly.

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The ocular surface changes of keratoconjunctivitis sicca (KCS) could be the result of the effect of an altered tear film on the epithelial environment. To evaluate the possibility of improving the environmental conditions of the ocular surface by lowering tear osmolarity, increasing tear film volume and stabilising the tear film. Also, to study the effect of such an improvement on the epithelial cells of the ocular surface. One hundred and thirty-five patients with a diagnosis of KCS were treated on a randomised basis with either unpreserved hypotonic 0.4% hyaluronic acid (HHA) eye drops or 0.3% hydroxypropylmethylcellulose plus 0.1% Dextran 70 (HPMC) eye drops 6 times a day for 60 or 90 days. In all patients a Schirmer I test, break-up time (BUT), ocular surface staining with 1% Bengal Rose, or 2% fluorescein, as well as subjective symptoms, were recorded before and 15, 30 and 60 days after the beginning of the study. Patients were divided into three subgroups and the effect of the treatment was studied using three different techniques: the tear ferning test, conjunctival impression cytology and tear osmolarity measurement. Improvements in BUT, vital staining, Schirmer I and symptoms were recorded in both groups of treatment, with significant differences for patients treated with 0.4% HHA. On day 60, 30 min after installation: tear ferning patterns changed from 100% pathological (types III-IV) to 93% physiological (types I-II) in the 0.4% HHA group and from 100% pathological to 78% physiological in the 0.3% HPMC group (p < 0.01 between groups). Tear osmolarity shifted from 353 +/- 23 to 305 +/- 6 mosmol/l in the 0.4% HHA group and from 346 +/- 15 to 336 +/- 8 mosmol/l in the 0.3% HPMC group (p < 0.001 between groups). On day 90, the impression cytology score improved from 1.2 to 1.9 in the 0.4% HHA group while it did not change in the 0.3% HPMC group (p < 0.05 between groups). In KCS appropriate treatment with a hypotonic 0.4% HHA tear substitute can change the tear environment and results in improvement of the epithelial conditions of the ocular surface.

The purpose of this study was to evaluate the efficacy of LO2A, a newly developed tear substitute containing glycerine and sodium hyaluronate, in the treatment of dry eyes. Twenty-five informed consent patients suffering from keratoconjunctivitis sicca were included. Patients were treated for one week with LO2A in one eye, and with their current tear substitute in the other eye. Rose bengal staining was evaluated on a scale of 0 to 3. Patient satisfaction was graded on a scale of 1 to 5. The average satisfaction score for LO2A was significantly higher compared to the control preparations at 1 week (p=0.0003) and at 2 weeks (p=0.0232). A highly significant reduction in rose bengal staining was demonstrated following 1 week of treatment with LO2A (p<0.0001). The LO2A treated eyes had significantly less staining than control eyes at 1 week (p=0.021) and at 2 weeks (p=0.023). An inverse correlation was found between patient grading and the rose bengal scoring (spearman rank coefficient = -0.49, p<0.001). LO2A showed a beneficiary effect on dry eye patient satisfaction and on rose bengal test, as compared to other tear substitute preparations currently used by these patients.

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Solutions of hydroxypropylmethylcellulose (HPMC) and polyvinyl alcohol (PVA) are widely used as artificial tears. However, their usefulness is limited by the short duration of their effect. Dilute sodium hyaluronate (SH) solutions exhibit non-Newtonian rheology with high viscosities at low shear rates, which would be expected to enhance their ocular surface residence time. Using quantitative gamma scintigraphy, estimates of the ocular surface residence times of 0.3% HPMC, 1.4% PVA, and 0.2% SH were made in six patients with keratoconjunctivitis sicca. The sodium hyaluronate solution had a mean half-life on the ocular surface of 321 s, significantly longer than hydroxypropylmethylcellulose (44 s; p = 0.012) and polyvinyl alcohol (39 s; p = 0.013).

The effect of sustained-release artificial tear inserts on symptoms and signs of reduced tear production in keratoconjunctivitis sicca (KCS) was evaluated in an open clinical trial including 30 patients. A significant relief of sicca symptoms and a decrease in keratoconjunctival staining were seen in 10 patients fulfilling the study, whereas no significant effect on Schirmer test and tear break-up-time could be detected, neither in patients with pure KCS nor with KCS as a manifestation of Sjögren's syndrome. Twenty patients (67%) withdrew due to adverse effects, which were reported in total 80% of the patients. Absence of measurable tear secretion predicted treatment failure. Due to the frequent side effects, the artificial tear inserts cannot be recommended as a first line treatment in KCS patients.

Twenty patients with keratoconjunctivitis sicca used three different viscoelastic tear formulations and a polyvinyl alcohol artificial tear for two weeks each. Each formulation was used once every two waking hours in a controlled double-masked study. Eighteen patients reported marked improvement over the course of the study, in terms of the severity of itching, burning, and foreign body sensation. Corneal staining and mucous strand formation were also reduced in patients with these manifestations. No formulation was preferred by a majority of patients or proved superior in treating signs of keratoconjunctivitis sicca. However, patients with low Schirmer test scores uniformly preferred a solution containing chondroitin sulfate, while patients with moderate Schirmer test scores tended to prefer a solution of polyvinyl alcohol or hyaluronic acid.

The mucolytic agent bromhexine in 0.2% solution in eye drops form was compared with 0.5% methyl cellulose eye drops in a controlled single-blind crossover study involving 24 volunteers (seven men and 17 women) in whom sicca syndrome had been diagnosed on the basis of the lysozyme test. There was no statistically significant difference between the volunteers' preferences for one of the two products or in the objective parameters, i.e. the lysozyme test, the bengal red rating scale and Schirmer's test. Seven subjects showed a distinct preference for treatment with Dakryo Biciron and six patients preferred methyl cellulose; the remaining patients had no special preference for either of the two drugs. The preference for one of the two drugs could not be correlated with the values of the objective parameters.

We have studied the effect of the aluminum complex of sucrose sulphate (Sucralfate suspension) and the sodium salt of sucrose sulphate (sodium sucrose sulphate solution) on patients with keratoconjunctivitis sicca. Eyes treated with either of these two drugs showed a decrease in painfulness and blurring of vision. On examination the surface area of the corneal lesions, stained with fluorescein, diminished during treatment. As for the difference in effect between the two eyedrops, the solution was better tolerated.

The effect upon the tear film of a new tear substitute, Dacriosol, was compared to a non-viscous solution, saline, an to a highly viscous solution, Isopto Plain, in 15 normal healthy subjects and in 15 patients with mild to moderate keratoconjunctivitis sicca. No differences between the test solutions could be measured 3 h after last medication regarding: Schirmer's test, break-up time, rose bengal staining, corneal sensitivity and tear content of lysozyme. The test persons could not discriminate subjectively between the effect of the test solutions. The investigation parameters show an equal effect of Dacriosol, Isopto Plain and saline both in normal healthy subjects and in patients with keratoconjunctivitis sicca.

Metformin is known to lower inflammation, independent of its anti-diabetic action. Thus, topical metformin can be a therapeutic strategy for managing ocular inflammation associated with diabetes. To achieve this and address the issues of ocular retention and controlled release an in situ gel of metformin was developed. The formulations were prepared using sodium hyaluronate, hypromellose, and gellan gum. The composition was optimized by monitoring gelling time/capacity, viscosity, and mucoadhesion. MF5 was selected as the optimized formulation. It showed both chemical and physiological compatibility. It was found to be sterile and stable. MF5 exhibited sustained release of metformin for 8h that fitted best with zero-order kinetics. Further, the release mode was found to be close to the Korsmeyer-Peppas model. Supported by an ex vivo permeation study, it showed potential for prolonged action. It showed a significant reduction in ocular inflammation that was comparable to that of the standard drug. MF5 shows translational potential as a safe alternative to steroids for managing ocular inflammation.

Polymer mucoadhesive films being developed for use in ophthalmology represent a new tool for drug delivery and are considered an alternative to traditional dosage forms. Due to their mucoadhesive properties, carrageenans (CRGs) are widely used in various forms for drug delivery. In this study, films based on CRGs of various structural types (κ/β, κ, x, and λ) for use in ophthalmology were studied. The films were loaded with the active substance echinochrome (ECH), a sea urchin pigment used in ophthalmology. Spectral data showed that ECH remained stable after its incorporation into the CRG films and did not oxidize for at least six months. Hydrophilic CRG films with a thickness of 10-12 µm were characterized in terms of their swelling and mucoadhesive properties. The rheological properties of solutions formed after film dissolution in artificial tears were also assessed. κ- and κ/β-CRG films with ECH exhibited pseudoplastic behavior after rehydrating films with an artificial tear solution. The CRG-loaded films had different swelling characteristics depending on the structure of the CRG used. The films based on highly sulfated CRGs dissolved in artificial tears, while the films of low-sulfated κ/β-CRG exhibited limited swelling. All studied ECH-loaded films exhibited mucoadhesive properties, which were evaluated by a texture analyzer using mucous tissue of the small intestine of the pig as a model. There was a slight prolongation of ECH release from CRG films in artificial tears. The effect of CRG/ECH on the epithelial cell lines of the outer shell of the human eye was investigated. At low concentrations, ECH in the composition of the CRG/ECH complex had no cytotoxic effect on corneal epithelial and conjunctival human cells. The use of ECH-containing films can prevent the drug from being immediately washed away by tears and help to retain it by increasing viscosity and having mucoadhesive properties.

Topical instillation of drugs targeting the posterior ocular segment is an expanding area of research. Chitosan and hyaluronic acid have remarkable mucoadhesive properties and potentially enhance pre-corneal retention time after topical instillation. Bearing this in mind, we explored the possibility of delivering epoetin beta (EPOβ) to the posterior segment of the eye in a chitosan-hyaluronic acid (CS/HA-EPOβ) nanoparticulate system using the topical route of administration. Complete ophthalmological examinations, electroretinography and microhematocrit evaluations were performed in Wistar Hannover (WH) rats, before and after topical administration of nanoparticles. The right eye received CS/HA-EPOβ and the left eye received only empty nanocarriers (control). Animals were split into 6 groups and at designated timepoints, all animals from each group (n = 3) were euthanized and both eyes enucleated. Retinal morphology and EPOβ ocular distribution were assessed, respectively, through hematoxylin and eosin (HE) and immunofluorescence staining. After topical administration, no adverse ocular signs were noted and no significant changes either in microhematocrits nor in electroretinographies were detected. During the study, intraocular pressure (IOP) was always kept within physiological range bilaterally. No histological changes were detected in any of the ocular globes. Immunofluorescence enabled the identification of EPOβ in the retina 12 h after the administration, its presence still being detectable at day 21. In conclusion, CS/HA nanoparticles could efficiently deliver EPOβ to the retina of WH rats after topical instillation, being considered biologically safe. Topical administration of this nanoformulation could be a valuable tool for retinal neuroprotection, decreasing risks associated with more invasive routes of administration, being cost effective and also increasing long-term patients' compliance.

Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic applications owing to its unique properties of biocompatibility, biodegradation, and viscoelasticity. HA being a natural component of eye tissue with significant role in wound healing is a natural choice as a carrier for ocular drug delivery, provided the incorporated drugs are released in a sustained manner. However, localized sustained release of drugs inside eye has been difficult to achieve because of the inability to retain carriers for long periods in the eye. Using noncrosslinked (soluble) HA offers limited control over site retention of drugs. In order to obtain prolonged sustained delivery, two HA-based composite hydrogels incorporating nanocarriers, have been synthesized and characterized for swelling, rheology, degradation, and in vitro release of latanoprost, a drug used to reduce intraocular pressure. The HA is first chemically modified, mixed with drug-loaded liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro release study shows longer sustained release of latanoprost from composite hydrogels as compared to liposomes or hydrogels alone indicating additional resistance to drug diffusion because of the incorporation of liposomes inside the hydrogels. It is believed that these nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases.