离心法制备胶原膜载释氟康唑治疗兔眼真菌性角膜炎的研究

目的 研究用离心法制得的角膜胶原膜载释氟康唑(普芬)眼液在兔眼真菌性角膜炎治疗中的应用.方法 从猪巩膜中提取、纯化胶原,采用离心法制备角膜胶原膜,在普芬眼液内浸泡用于治疗兔眼真菌性角膜炎.结果 胶原膜载释普芬眼液治疗组病灶愈合平均时间11 d,局部滴用普芬眼液组病灶愈合平均时间18 d,两组治愈率和有效率分别为78.94%、63.15%和92.10%、78.94%,差异有统计学意义(P<0.05).结论 应用离心法制得的胶原膜载释普芬眼液是治疗真菌性角膜炎给药途径的创新,具有广阔的发展前景.     

Effectiveness of heparin eye drops in paraquat-induced ocular injury

Purpose: To evaluate the efficacy of heparin eye drops in the treatment of paraquat-induced ocular surface injury.

Design and methods: In this retrospective study, we included 25 patients (31 eyes) with paraquat-induced ocular surface injury, who attended the Affiliated Hospital of Weifang Medical University between October 2008 and October 2013. The patients were split into two groups according to whether or not received heparin eye drops. The clinical data were compared between the two groups, i.e. clinical histories, results of examinations, treatments and outcomes.

Results: Eleven patients (group A, 15 eyes) received prompt irrigation with 0.9% saline every two hours, 0.1% pranoprofen eye drops four times a day, 20% autologous serum every two hours, recombinant bovine basic fibroblast growth factor eye-gel two times a day, oral vitamin C 2.0?g and prednisone 30?mg daily. Fourteen patients (group B, 16 eyes) received additional treatment with heparin eye drops. Ten eyes in group A and seven eyes in group B developed a pseudomembrane on the ocular surface at significantly different rate (mean?±?SD) of 1.20?±?1.01 and 0.43?±?0.51, respectively (t?=?2.66, p?=?0.01). Seven eyes among 10 had a pseudomembrane reoccurred in group A while none had a pseudomembrane reoccurred in group B (Fisher’s exact test, p?=?0.01). No significant differences were seen in the duration of epithelial recovery between the two groups: 15.13?±?5.13 days in group A and 16.81?±?5.56 days in group B (t?=?0.87, p?=?0.39). After the treatment, mild corneal opacity and pannus were observed in five patients of group A and four patients of group B, without any significant difference between the two groups (p?=?0.70).

Conclusions: The paraquat-induced ocular surface injury observed in this case series was characterized by the formation of conjunctival pseudomembrane with good prognosis and mild complications. Heparin eye drops reduce the occurrence, especially the reoccurrence of pseudomembrane. Further studies are warranted.     

Safety and efficacy of autologous serum eye drop for treatment of dry eyes in graft-versus-host disease

Purpose: To evaluate the treatment of autologous serum eye drops (ASED) on dry eyes in patients with graft-versus-host disease (GVHD).

Methods: A retrospective chart review of 35 patients with a history of ocular GVHD following hematopoietic stem cell transplantation that used ASED to alleviate dry eye symptoms was performed. Patients were categorized into three different groups. If patients had available ophthalmic data before and after starting treatment was group 1 (n?=?14), had available ophthalmic data after starting treatment in group 2 (n?=?10) and had available ophthalmic data before treatment or did not have any data after starting treatment in group 3 (n?=?11). Data were collected on patient’s age, gender, primary diagnosis, visual acuity and fluorescein corneal staining were collected on individual eyes in order to evaluate the efficacy of the ASED on alleviating dry eye-related signs and symptoms.

Results: No adverse ocular effect from the ASED was found in our series (except one fungal keratitis). All patients reported either improvement (55%) or stability (45%) in their ocular symptoms upon the use of ASED. In patients with available data before and after starting treatment, the corneal staining score improved by a median of 1 (p?=?0.003) and the LogMAR visual acuity had a non-significant improvement.

Conclusion: In our study, ASED used by patients with ocular GVHD were both safe and effective. ASED should be considered in patients with GVHD who suffer from dry eyes.     

那他霉素联合氟康唑治疗外伤后真菌性角膜炎的疗效观察

目的探讨5%那他霉素滴眼液联合0.2%氟康唑滴眼液和氟康唑注射液治疗外伤后真菌性角膜炎的临床疗效及预后情况。方法选取2011年6月—2015年6月重庆市长寿区人民医院收治入院的外伤后真菌性角膜炎患者180例为研究对象,按随机数字表法将患者分为对照组和治疗组,每组各90例。对照组给予0.2%氟康唑滴眼液1~2滴/次,角膜病变轻度者1次/h,中度及重度者1次/0.5 h,同时给予氟康唑注射液1 m L结膜下注射,1次/d。治疗组在对照组的基础上加用5%那他霉素滴眼液交替点眼1~2滴/次,1次/1 h。两组均治疗2~3周。观察两组的临床疗效,同时比较治疗前后两组患者的角膜炎严重程度评分、视力以及随访90 d的预后情况。结果对照组、治疗组患者总有效率分别为73.3%、88.9%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后7、14 d,两组患者角膜炎严重程度评分显著降低,同组治疗前后差异具有统计学意义(P0.05);且治疗组这些观察指标的降低程度优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后两组总体视力均明显改善,同组治疗前后差异具有统计学意义(P0.05);且治疗组总体视力改善情况优于对照组,两组比较差异有统计学意义(P0.05)。随访90 d,对照组、治疗组预后中等以上比率分别为85.5%、96.7%,两组预后中等以上比率比较差异具有统计学意义(P0.05)。结论 5%那他霉素滴眼液联合0.2%氟康唑滴眼液和氟康唑注射液治疗外伤后真菌性角膜炎具有较好的疗效,能够显著降低角膜炎严重程度评分,明显改善患者视力和预后水平,值得临床运用和推广。     

Corneal antinociceptive effect of (-)-α-bisabolol

Context: (-)-α-Bisabolol (BISA) is a sesquiterpene alcohol widely used as scent in cosmetic preparations, perfumes, shampoos, toilet soaps and other toiletries with potential for use in the pharmaceutical area.

Objective: To evaluate the corneal antinociceptive efficacy of BISA and to analyze the best solubilizing agent.

Materials and methods: Acute corneal nociception was induced by the local application of hypertonic saline (5 M NaCl; 20?μL) to the corneal surface of Swiss mice (n?=?8/group) 60?min after topical treatment with solutions or ointment containing BISA (50–200?mg/mL). The number of eye wipes performed with the ipsilateral forepaw was counted for a period of 30?s. Control groups (vehicles) were included.

Results: BISA (50, 100 or 200?mg/mL) solubilized with Tween 80 did not reduce the number of eye wipes. Animals treated with the ointment (BISA 50, 100 or 200?mg/mL; p?p?Discussion and conclusion: BISA possess corneal antinociceptive activity. Although the ointment presented antinociceptive effect, it is concluded that BISA when associated with propylene glycol has better potential for corneal nociceptive pain since it is more comfortable to use, leading to greater acceptance by patients.     

氟康唑联合碘酊治疗真菌性角膜炎的疗效观察

目的观察氟康唑联合碘酊治疗真菌性角膜炎的临床疗效。方法真菌性角膜炎患者68例,按就诊顺序随机分为观察组和对照组,各34例。观察组采用氟康唑联合碘酊治疗;对照组采用两性霉素B治疗;治疗后观察2组疗效。结果氟康唑联合碘酊治疗真菌性角膜炎的临床疗效明显优于两性霉素B治疗,差异有统计学意义（P〈0.05）。结论氟康唑联合碘酊治疗真菌性角膜炎疗效显著,不良反应小,值得推广应用。     

氟康唑局部应用治疗真菌性角膜溃疡

目的 :探讨氟康唑局部应用治疗真菌性角膜溃疡的疗效。方法 :对 2 6例 [男性 18例 ,女性 8例 ,年龄 (44±s 10 )a ,2 1～ 5 6a]真菌性角膜溃疡病人 ,应用 0 .2 %氟康唑静脉注射液行球结膜下注射 ,0 .5mL ,qd ,5d一个疗程。第 2疗程根据病情 2d或 3d球结膜下注射 1次 ,每次 0 .5mL ,并用该药滴眼 ,2h 1次 ,每次 1滴 (每滴 0 .0 5mL)。结果 :治愈 2 4例 ,有效 2例。结论 :氟康唑局部应用治疗真菌性角膜溃疡疗效确切且安全     

Topical and subconjunctival ranibizumab (lucentis) for corneal neovascularization in experimental rat model

Purpose: To compare the effectiveness of the topical and subconjunctival (SC) ranibizumab treatment in experimental corneal neovascularization (NV) model in rats.

Methods: A model of NV was generated by cauterizing right corneas of 30 Sprague-Dawley rats with silver nitrate. The animals were separated into five groups randomly. first group (control group) received topical artificial tear drops two times daily while second and third groups received topical ranibizumab four times daily at concentrations of 5?mg/mL and 10?mg/mL, respectively. Forth and fifth groups were given 0.5?mg/0.05?mL and 1?mg/0.1?mL of SC ranibizumab in the 1st, 3rd and 7th days. The measurements (percentage of NV area and number of vessels) from digital photographs of the corneas were determined and analyzed using analysis software (ImageJ, v1.38). The animals were sacrificed on the 10th day and their corneas were subjected to hemotoxylin-eosin histopathological staining and antisera against CD34 and von-Willebrand factor to evaluate microvascular structures immunohistochemically.

Results: The percentage of the corneal NV area and number of vessels in all treatment groups was found to be significantly lower than the control group. There was no significant difference in relation to the percentage of NV area and number of vessels in the treatment groups. Score of the corneal edema was determined to be significantly less in the groups that undertook treatment. Number of vessels and inflammatory cells were significantly lower in the histological and immunohistochemical sections in the treated groups than in the control group. In all treatment groups, fibroblast intensity was significantly lower than the control group (p?=?0.005).

Conclusion: Topical or SC administration of ranibizumab seems to be a promising and effective medication in the treatment of corneal NV. Further research is recommended to assess the potential side effects and effective dose.     

Novel mucoadhesive polysaccharide isolated from Bletilla striata improves the intraocular penetration and efficacy of levofloxacin in the topical treatment of experimental bacterial keratitis

Objectives The objective of the present study was to evaluate a novel mucoadhesive polymer extracted from Bletilla striata for ocular delivery of 0.5% levofloxacin in rabbits, and to determine its improved efficacy against experimental keratitis. Methods B. striata polysaccharide (BsP) was subjected to cell cytotoxicity and ferning tests. The pharmacokinetics and bioavailability of topically applied 0.5% levofloxacin‐BsP eye drops was investigated and compared with 0.5% levofloxacin eye drops (Cravit). Experimental Staphylococcus aureus keratitis was induced and treated with levofloxacin or levofloxacin‐BsP eye drops. Key findings BsP markedly increased the proliferative capacity of a human corneal endothelial cell line. The ferning test showed that BsP exhibited optimal performance as a tear fluid. The polysaccharides significantly increased intra‐aqueous penetration and corneal accumulation in rabbits. Treatment with levofloxacin‐BsP reduced the number of organisms more significantly than eye drops containing levofloxacin alone. Conclusions BsP appears to be a promising candidate as a vehicle for topical ophthalmic drug delivery, especially for antibiotics.     

高效液相色谱法测定氟康唑滴眼液的含量

目的建立一种采用高效液相色谱法测定氟康唑滴眼液含量的方法。方法色谱柱为Diamonsil Cl8不锈钢柱(250.0mm×4.6mm,5μm),流动相为磷酸盐缓冲液pH7.0-甲醇(55∶45),检测波长261nm,柱温20℃,流速1.0mL/min。结果样品中主药与其他物质分离良好;氟康唑检测浓度0.0992～0.992mg/mL范围内,与峰面积积分值线性关系良好(r=0.9999);平均回收率为99.87%(RSD=0.22%)。结论采用HPLC法操作方便、结果准确、专属性强、重现性好,适合氟康唑滴眼液的含量测定。     

Antifungal and antibacterial activities of different extracts of Harungana madagascariensis stem bark

The antifungal and antibacterial effects of the stem bark extracts of Harungana madagascariensis Lam. ex Poir. (Clusiaceae) were examined against nine microbial pathogens causing infections in both man and animals. Hexane (H), dichloromethane (D), chloroform (C), ethyl acetate (E), acetone (A), methanol (M), and water (W) extracts were tested in vitro through bioautography and minimum inhibitory concentrations (MIC) determination using the serial micro-dilution assays. Bioautographic results revealed the presence of eight different spots. Extract A exhibited the lowest MIC of 0.04?mg/mL against Microsporum canis, while water extract (W) and methanol (M) showed the highest MIC of 2.5?mg/mL against at least one of the tested fungi when compared to amphotericin B with 0.0625–1?g/mL. Sporotrichum schenckii was the most susceptible fungal pathogen with average MIC of 0.06?mg/mL, while the acetone extract (A) was the most active against three fungal organisms when compared with other extracts. Similarly, extracts D, C, E and A exhibited very high activity with low MIC values of 0.156–0.62?mg/mL, while M and W gave the highest values of 0.31–2.5?mg/mL on bacterial pathogens as compared to gentamicin (0.02–0.62 8?g/mL). The dichloromethane extract is the most active against bacteria with average MIC of 0.19?mg/mL, while Staphylococcus aureus is the most sensitive organism; that shows susceptibility at an average MIC of 0.34?mg/mL. These results provide promising information for the potential use of the crude extracts from the stem-bark of H. madagascariensis in the treatment of bacterial and fungal infections similar to what was obtained in the leaves.     

浅谈真菌性角膜炎的药物治疗临床分析

目的 回顾性总结真菌性角膜溃疡的有效药物治疗的临床表现、病程及治愈率。方法30例（32只眼）患者真菌性角膜溃疡临床表现符合诊断标准。治疗上采用抗生素，如庆大霉素结膜下注射，同时用抗生素及抗真菌剂滴眼（1％5-氟胞嘧啶和0．1～0．3％两性霉素B），加强散瞳治疗。急性期在肝功能正常情况下，可口服抗真菌药（酮康唑）1～3疗程；多种维生素族药物口服，坚持全疗程；2．5％碘酊小病灶早期烧灼，或大病灶的中晚期烧灼，一般不超过3次。结果30例（32只眼）经药物治疗，其中21只眼3～10周溃疡治愈，其余11只眼疗程为3～5个月。合并症病例因病灶穿孔后新生血管深入而愈合。结论真菌性角膜溃疡。早期诊断，早期合理用药是治愈的关键。小病灶、表浅者用抗真菌剂并及时病灶烧灼效果肯定，预后留有浅层斑翳；治疗期均禁用激素，病灶愈合后仍应巩固用药1月以上。     

Anti-cryptococcal activity of ethanol crude extract and hexane fraction from Ocimum basilicum var. Maria bonita: mechanisms of action and synergism with amphotericin B and Ocimum basilicum essential oil

Context: Ocimum basilicum L. (Lamiaceae) has been used in folk medicine to treat headaches, kidney disorders, and intestinal worms.

Objective: This study evaluates the anti-cryptococcal activity of ethanol crude extract and hexane fraction obtained from O. basilicum var. Maria Bonita leaves.

Materials and methods: The MIC values for Cryptococcus sp. were obtained according to Clinical and Laboratory Standards Institute in a range of 0.3–2500?μg/mL. The checkerboard assay evaluated the association of the substances tested (in a range of 0.099–2500?μg/mL) with amphotericin B and O. basilicum essential oil for 48?h. The ethanol extract, hexane fraction and associations in a range of 0.3–2500?μg/mL were tested for pigmentation inhibition after 7?days of treatment. The inhibition of ergosterol synthesis and reduction of capsule size were evaluated after the treatment with ethanol extract (312?μg/mL), hexane fraction (78?μg/mL) and the combinations of essential oil?+?ethanol extract (78?μg/mL?+?19.5?μg/mL, respectively) and essential oil?+?hexane fraction (39.36?μg/mL?+?10?μg/mL, respectively) for 24 and 48?h, respectively.

Results: The hexane fraction presented better results than the ethanol extract, with a low MIC (156?μg/mL against C. neoformans T₄₄₄ and 312?μg/mL against C. neoformans H99 serotype A and C. gattii WM779 serotype C). The combination of the ethanol extract and hexane fraction with amphotericin B and essential oil enhanced their antifungal activity, reducing the concentration of each substance needed to kill 100% of the inoculum. The substances tested were able to reduce the pigmentation, capsule size and ergosterol synthesis, which suggest they have important mechanisms of action.

Conclusions: These results provide further support for the use of ethanol extracts of O. basilicum as a potential source of antifungal agents.     

Efficacy of bromovinyldeoxyuridine in the treatment of herpes simplex virus and varicella-zoster virus eye infections

As has been established in rabbits, (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) is superior to 5-iodo-2'-deoxyuridine (IDU) in the topical treatment of epithelial HSV-1 (herpes simplex virus type 1) keratitis, and superior to 5-trifluoromethyl-2'-deoxyuridine (TFT) in the topical treatment of deep stromal HSV-1 keratitis and HSV-1 uveitis. BVDU 0.1% eye drops have also proven efficacious in the treatment of patients with dendritic corneal ulcers, geographic corneal ulcers and stromal keratitis, and combined treatment of BVDU 0.1% eye drops with oral BVDU at 375 mg/day for 5 days led to a prompt healing of keratouveitis and skin lesions in patients with ophthalmic herpes zoster.     

Intrinsic cytotoxic effects of fluoroquinolones on human corneal keratocytes and endothelial cells

ABSTRACT

Objective: To determine the intrinsic cytotoxicity of five fluoroquinolones (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, ofloxacin) on human corneal keratocytes (HCK) and human corneal endothelial cells (HCE).

Research design and methods: Cultures of replicating HCK and HCE were exposed to ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, or ofloxacin concentrations of 1?mg/mL, 100?μg/mL, 10?μg/mL, 1?μg/mL, 100?ng/mL, or 10?ng/mL for 15, 30, 60, or 240?min. Each of the 24 fluoroquinolone concentration–time exposures was tested against its own serum-free minimal essential medium (MEM) control. Cell number was quantified with a fluorescence bioassay.

Main outcome measure: Cytotoxicity was defined as a significant (?p < 0.05) difference in cell number measured as mean calcein fluorescence product versus control for each fluoroquinolone concentration–time exposure.

Results: Fluoroquinolone-induced cytotoxicity was concentration- and time-dependent in HCK and HCE cultures. The number of cytotoxic concentration–time exposures was highest with ciprofloxacin (23 of 24 exposures in HCK and 24 of 24 exposures in HCE) and lowest with levofloxacin (10 of 24 exposures in both HCK and HCE).

Conclusions: In vitro cell cultures are useful for evaluating cell response to potentially toxic insults, although cell cultures may lack tissue components that may prevent or ameliorate damage in vivo. In this assay, fluoroquinolones displayed the potential to be cytotoxic to human corneal keratocytes and endothelial cells, depending on drug concentration and duration of exposure. The potential for cytotoxicity may differ among fluoroquinolones.     

两性霉素B脂质体滴眼液在兔房水中的药动学

目的:探索兔眼局部应用生物黏附性两性霉素B脂质体(AmBL)滴眼液后,房水中的药动学状况。方法:32只新西兰白兔,在角膜上皮完整和刮除时,分别应用0．5％AmBL滴一眼,用0．5％两性霉素B滴眼液(AmBS)滴对侧眼作对照,于用药后0．25,0．5,1,2,3和4 h的6个时点,选取不同的白兔抽取房水,用高效液相色谱法测定房水中AmB的含量。结果:AmBL滴眼后,房水中AmB的有效抑菌浓度可维持2 h,AmBE S滴眼1 h后即近全部消除。角膜上皮完整时,AmBL的AUC和t1/2是AmBS的3．6倍和5倍;角膜上皮刮除后,AmBL的AUC和t1/2是AmBL S的3．9倍和3．2倍。结论:0．5％AmBL滴眼液具有较好的缓释作用和生物利用度,药物浓度较稳定,作用时间较长,是较有前途的局部治疗真菌性角膜炎的新型缓释制剂。     

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections

Background: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration.

Methods: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3?months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale.

Results: A total of 90 patients were included in the study. 43.3% n?=?39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n?=?11 amongst study eyes vs 4.4%, n?=?4 amongst control, fellow eyes (p?p?=?0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p?=?0.02).

Conclusion: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.     

人血浆纤维结合蛋白治疗角膜炎

目的 :观察人血浆纤维结合蛋白治疗角膜炎的疗效。方法 :角膜炎病人 12 8例 ,分为治疗组 54例 ( 61眼 ) ,男性 31例 ,女性 2 3例 ,年龄 4 2±s 17a ,给予人血浆纤维结合蛋白点眼 6～ 8次 /d ,2滴 /次。对照组 74例 ( 82眼 ) ,男性 4 7例 ,女性 2 7例 ,年龄37± 15a ,给予常规眼药水点眼 6～ 8次 /d ,2滴 /次。 2组均以 15d为一个疗程。结果 :人血浆纤维结合蛋白治疗组有效率达 77% ,对照组有效率达4 9 % (P <0 .0 1)。结论 :人血浆纤维结合蛋白治疗角膜炎疗效满意     

Endophytic fungi associated with Taxus fuana (West Himalayan Yew) of Pakistan: potential bio-resources for cancer chemopreventive agents

Context: Endophytic fungi, being a prolific source of bioactive secondary metabolites, are of great interest for natural product discovery.

Objective: Isolation and partial characterization of endophytic fungi inhabiting the leaves and woody parts of Taxus fuana Nan Li & R.R. Mill. (Taxaceae) and evaluation of biological activity.

Materials and methods: Endophytic fungal isolates were identified by molecular analysis of internal transcribed spacer (ITS) regions of 18S rDNA. Extracts of the endophytic fungi cultured on potato dextrose agar and modified medium were evaluated using cancer chemoprevention bioassays [inhibition of TNF-α-induced NFκB, aromatase and inducible nitric oxide synthase (iNOS); induction of quinone reductase 1 (QR1)] and growth inhibition with MCF-7 cells.

Results: Nine of 15 fungal isolates were identified as belonging to Epicoccum, Mucor, Penicillium, Chaetomium, Paraconiothriym, Plectania or Trichoderma. Five of the 15 extracts inhibited NFκB activity (IC₅₀ values ranging between 0.18 and 17?μg/mL) and five inhibited iNOS (IC₅₀ values ranging between 0.32 and 12.9?μg/mL). In the aromatase assay, only two isolates mediated inhibition (IC₅₀ values 12.2 and 10.5?μg/mL). With QR1 induction, three extracts exhibited significant activity (concentrations to double activity values ranging between 0.20 and 5.5?μg/mL), and five extracts inhibited the growth of MCF-7 cells (IC₅₀ values ranging from 0.56 to 17.5?μg/mL). Six active cultures were derived from woody parts of the plant material.

Conclusion: The endophytic fungi studied are capable of producing pharmacologically active natural compounds. In particular, isolates derived from the wood of Taxus fuana should be prioritized for the isolation and characterization of bioactive constituents.     

Topical hyaluronan alone promotes corneal epithelial cell migration whereas combination with benzalkonium chloride impairs epithelial wound healing

Abstract

Purpose: To evaluate the effects of topical hyaluronan (HA) on corneal epithelial wound healing when administered with or without benzalkonium chloride (BAC).

Methods: A cultured human corneal epithelial cell line (HCE-T) was subjected to in vitro scratch assays and in situ epithelial migration was evaluated in organ-cultured rabbit corneas. The corneal epithelium of C57BL/6J mice was also evaluated to determine in vivo wound healing. An in vivo imaging system was also used to evaluate the effects of HA on eye drop retention on the ocular surface.

Results: The findings revealed the promotion of HCE-T migration, in situ rabbit corneal epithelial migration, and in vivo wound healing in mouse corneal epithelium by HA. Pre-treatment with HA also protected against delayed epithelial wound healing in BAC in vitro. However, pre-treatment with 3?mg/mL HA did not show a protective effect against BAC in vivo, but instead delayed epithelial wound healing and increased detection of cleaved caspase-3. This suggested that HA promotes the retention of BAC on the ocular surface. The instilled HA was retained after 15?min, at a significantly higher rate than for phosphate-buffered saline.

Conclusions: The combination of HA and BAC impaired wound healing in the corneal epithelium.