[Show abstract][Hide abstract] ABSTRACT: to test the effectiveness of breast feeding (BF), music therapy (MT), and combined breast feeding and music therapy (BF+MT) on pain relief in healthy-term neonates during heel lance.Designrandomised controlled trial.Settingin the postpartum unit of one university-affiliated hospital in China from August 2013 to February 2014.Participantsamong 288 healthy-term neonates recruited, 250 completed the trial. All neonates were undergoing heel lancing for metabolic screening, were breast fed, and had not been fed for the previous 30 minutes.Interventionsall participants were randomly assigned into four groups – BF, MT, BF+MT, and no intervention – with 72 neonates in each group. Neonates in the control group received routine care. Neonates in the other three intervention groups received corresponding interventions five minutes before the heel lancing and throughout the whole procedure.MeasurementsNeonatal Infant Pain Scale (NIPS), latency to first cry, and duration of first crying.Findingsmean changes in NIPS scores from baseline over time was dependent on the interventions given. Neonates in the BF and combined BF+MT groups had significantly longer latency to first cry, shorter duration of first crying, and lower pain mean score during and one minute after heel lance, compared to the other two groups. No significant difference in pain response was found between BF groups with or without music therapy. The MT group did not achieve a significantly reduced pain response in all outcome measures.ConclusionsBF could significantly reduce pain response in healthy-term neonates during heel lance. MT did not enhance the effect of pain relief of BF.Implications for practicehealthy-term neonates should be breast fed to alleviate pain during heel lance. There is no need for the additional input of classical music on breast feeding in clinic to relieve procedural pain. Nurses should encourage breast feeding to relieve pain during heel lance.
[Show abstract][Hide abstract] ABSTRACT: Using anterior chamber optical coherence tomography to evaluate changes in angle anatomy in patients with primary angle-closure glaucoma (PACG) before and after trabeculectomy.
[Show abstract][Hide abstract] ABSTRACT: Abstract Purpose: To evaluate meibomian gland (MG) alterations in patients with primary chronic dacryocystitis (PCD) by in vivo confocal microscopy (IVCM), and to correlate the finding with clinical presentation. Methods: Twenty-eight eyes with the diagnosis of PCD and their contralateral unaffected eyes were studied and compared with 27 normal controls. All subjects completed an Ocular Surface Disease Index questionnaire (OSDI) and underwent slit-lamp biomicroscopy examination, tear break-up time (BUT) measurements, fluorescein staining, Schirmer test I, and an IVCM examination of the MG. IVCM parameters, including the MG acinar unit density (MGAUD), periglandular inflammatory cell density (ICD), MG acinar unit longest diameter (MGALD), and MG acinar unit shortest diameter (MGASD) and their correlation with clinical data were analyzed. Results: The mean MG expressibility scores, BUT values, and staining scores were significantly worse in eyes with PCD compared with the contralateral clinically unaffected eyes and controls (p < 0.05). A significant decrease in MGAUD was observed in PCD eyes compared with the controls and the contralateral clinically unaffected eyes. Conversely, the mean ICD and MGASD values were significantly higher in the PCD eyes. There were no significant differences in mean MGALD value between the PCD eyes and the contralateral clinically unaffected eyes. In addition, there were significant changes in the IVCM parameters in the contralateral unaffected eyes compared with the controls, including MGAUD, ICD, MGALD, and MGASD. All IVCM parameters showed a strong, significant correlation with MG dropout grades, MG expressibility, fluorescein staining scores, and OSDI values (all p < 0.05). Conclusions: Patients with unilateral PCD demonstrated significant changes in MG as compared with the contralateral clinically unaffected eyes and controls. The MG function should be closely observed in these patients.
[Show abstract][Hide abstract] ABSTRACT: Dry eye is a multifactorial disease of the tears and the ocular surface. This study aimed to investigate the clinical efficacy of a non-steroidal anti-inflammatory drug, pranoprofen, in the treatment of dry eye.
Chinese medical journal. 07/2014; 127(13):2407-12.
[Show abstract][Hide abstract] ABSTRACT: A 56-year-old woman with a history of disposable soft contact lens wear was referred to our university eye center for a corneal ulcer. Based on the microbial culture, the initial diagnosis was bacterial keratitis, which was unresponsive to topical fortified antibiotics. The patient was then examined using in vivo confocal microscopy, which revealed Acanthamoeba infection. This case emphasizes the need to suspect Acanthamoeba infection in soft contact lens wearers who present with progressive ulcerative keratitis or progressively worsening corneal ulcers that are not responsive to the usual antimicrobial therapy. It is also important to consider the possibility of a coinfection with bacterial and Acanthamoeba species.Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5168343391150859.
[Show abstract][Hide abstract] ABSTRACT: Benzalkonium chloride (BAC) is the most commonly used preservative in ophthalmic preparations.So far large bodies of clinical and experimental studies have shown that use of topical drugs containing BAC can induce a series of ocular surface diseases, such as apoptosis.However, recently, some clinical studies have shown that ocular toxicity in patients treated with eye drops containing BAC has not apparent correlated with BAC.Some scholars consider that the limitations of the research lead people to recognize the BAC toxicity exaggeratedly.Here we summarize numerous clinical and experimental studies of BAC in the past few years, and focus on reviewing recent researches of the toxic effect of BAC on ocular surface.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 04/2014; 50(4):303-6.
[Show abstract][Hide abstract] ABSTRACT: To determine the vision-related quality of life (VR-QOL) in patients with infectious keratitis using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25).
Sixty-five patients with infectious keratitis (IK) were enrolled in the study. The NEI VFQ-25 scores and clinical and demographic data, including age, gender, pathogen, best corrected visual acuity (BCVA), and duration of the disease, were collected from the subjects. The subscale and composite scores were calculated and analyzed. Correlations between the VFQ-25 scores and the clinical and demographic features were also explored.
The mean age of enrolled subjects was 48.4 years (SD, 16.2), with 44 males (67.7%). The microbial pathogens were viruses (n = 48, 73.8%), fungi (n = 13, 20.0%), and bacteria (n = 4, 6.2%). The mean scores of each VFQ-25 subscale ranged from 31.9 (SD, 28.6) for role difficulties to 92.7 (SD, 13.1) for color vision; the mean composite score was 58.1 (SD, 19.2). Significant differences in scores were observed only in the subscale of dependency among educational levels and in the mental health subscale and the composite among the three pathogen groups. Multivariate regression analysis revealed that VFQ-25 composite score correlated significantly with the BCVA of the worse-seeing eye, duration of the disease, history of operation (for IK treatment), and gender.
Infectious keratitis has extensive impacts on patients and VR-QOL. The BCVA of worse-seeing eye, duration, history of operation for IK treatment, and gender contributed independently to VR-QOL. Early treatment should be encouraged to obtain better visual prognosis and VR-QOL for patients with IK.
Optometry and vision science: official publication of the American Academy of Optometry 01/2014; · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We recently demonstrated that SERPINA3K, a serine proteinase inhibitor, has antioxidant activity in the cornea. Here we investigated the antioxidant effects of SERPINA3K on the pterygial, which is partially caused by oxidative stress in pathogenesis. The head part of primary pterygial tissue was dissected and then cultured in keratinocyte serum-free defined medium (KSFM). The cultured pterygial epithelial cells (PECs) were treated with SERPINA3K. The cell proliferation and migration of PECs were measured and analyzed. Western blot and quantitative real-time polymerase chain reaction (PCR) assay were performed. It showed that SERPINA3K significantly suppressed the cell proliferation of PECs in a concentration-dependent manner, compared with cultured human conjunctival epithelial cells. SERPINA3K also inhibited the cell migration of PECs. Towards its underlying mechanism, SERPINA3K had antioxidant activities on the PECs by significantly inhibiting NADPH oxidase 4 (NOX4), which is an important enzyme of ROS generation, and by elevating the levels of key antioxidant factors of ROS: such as NAD(P)H dehydrogenase (quinone 1) (NQO1), NF-E2-related factor-2 (NRF2) and superoxide dismutases (SOD2). Meanwhile, SERPINA3K down-regulated the key effectors of Wnt signaling pathway: β-catenin, nonphospho-β-catenin, and low-density lipoprotein receptor-related protein 6 (LRP6). We provided novel evidence that SERPINA3K had inhibitory effects on pterygium and SERPINA3K played antioxidant role via regulating the ROS system and antioxidants.
PLoS ONE 01/2014; 9(10):e108859. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There are several animal models illustrating dry eye pathophysiology. Current study would like to establish an ex vivo tissue culture model for characterizing dry eye. Human conjunctival explants were cultured under airlift or submerged conditions for up to 2 weeks, and only airlifted conjunctival cultures underwent increased epithelial stratification. Starting on day 4, the suprabasal cells displayed decreased K19 expression whereas K10 keratin became evident in airlift group. Pax6 nuclear expression attenuated already at 2 days, while its perinuclear and cytoplasmic expression gradually increased. MUC5AC and MUC19 expression dramatically decreased whereas the full thickness MUC4 and MUC16 expression pattern disappeared soon after initiating the airlift condition. Real time PCR showed K16, K10 and MUC16 gene up-regulated while K19, MUC5AC, MUC19 and MUC4 down-regulated on day 8 and day 14. On day 2 was the appearance of apoptotic epithelial and stromal cells appeared. The Wnt signaling pathway was transiently activated from day 2 to day 10. The inflammatory mediators IL-1β, TNF-α, and MMP-9 were detected in the conditioned media after 6 to 8 days. In conclusion, airlifted conjunctival tissue cultures demonstrated Wnt signaling pathway activation, coupled with squamous metaplasia, mucin pattern alteration, apoptosis and upregulation of proinflammatory cytokine expression. These changes mimic the pathohistological alterations described in dry eye. This correspondence suggests that insight into the pathophysiology of dry eye may be aided through the use of airlifted conjunctival tissue cultures.
PLoS ONE 01/2014; 9(1):e87368. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gap junction intercellular communication (GJIC) plays a critical role in the maintenance of corneal endothelium homeostasis. We determined if benzalkonium chloride (BAK) alters GJIC activity in the rabbit corneal endothelium since it is commonly used as a drug preservative in ocular eyedrop preparations even though it can have cytotoxic effects.
PLoS ONE 01/2014; 9(10):e109708. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prostaglandin (PG) analogs, including latanoprost, travoprost, and bimatoprost, are currently the most commonly used topical ocular hypotensive medications. The purpose of this study was to investigate the corneal alterations in rabbits following exposure to commercial solution of latanoprost, travoprost and bimatoprost. A total of 64 New Zealand albino rabbits were used and four groups of treatments were constituted. Commercial latanoprost, travoprost, bimatoprost or 0.02% benzalkonium chloride (BAK) was applied once daily to one eye each of rabbits for 30 days. The contralateral untreated eyes used as controls. Schirmer test, tear break-up time (BUT), rose Bengal and fluorescein staining were performed on days 5, 10, 20, and 30. Central corneal changes were analyzed by in vivo confocal microscopy, and the corneal barrier function was evaluated by measurement of corneal transepithelial electrical resistance on day 5. Whole mount corneas were analyzed by using fluorescence confocal microscopy for the presence of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, actin cytoskeleton, proliferative marker Ki67 and cell apoptosis in the epithelium. Topical application of commercial PG analogs resulted in significant corneal epithelial and stromal defects while no significant changes in aqueous tear production, BUT, rose bengal and fluorescein staining scores on day 5. Commercial PG analogs induced dislocation of ZO-1 and occludin from their normal locus, disorganization of cortical actin cytoskeleton at the superficial layer, and disruption of epithelial barrier function. The eyes treated with 0.02% BAK and latanoprost exhibited significantly reduced Schirmer scores, BUT, and increased fluorescein staining scores on days 10 and 30, respectively. Topical application of commercial PG analogs can quickly impair the corneal epithelium and stroma without tear deficiency. Commercial PG analogs break down the barrier integrity of corneal epithelium, concomitant with the disruption of cell junction and actin cytoskeleton between superficial cells in the corneal epithelium in vivo.
PLoS ONE 01/2014; 9(3):e89205. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the effects and mechanism of amniotic extraction on corneal healing after photorefractive keratectomy (PRK).
Experimental Study. Thirty-six New Zealand rabbit corneas were performed with PRK models (-10 diopters, 6.5 mm diameter). According to random number table, all eyes were divided into three groups, including treated with amniotic extraction, 0.1% dexamethasone and excipient respectively after operation. Clinical and histopathologic examinations were taken by slit-lamp microscope and light microscope. Corneal epithelium reparation was observed by fluorescent staining. Corneal stroma cell apoptosis was evaluated by terminal deoxyribonucleotidy transferase-mediated deoxynuridine triphophate nick end labeling (TUNEL) assay. Myofibroblast generation was evaluated by immunofluorescence checking the expression of alpha-smooth muscle actin (α-SMA). The number of TUNEL and α-SMA positive cells was analyzed to explore the effects on corneal haze. The haze grading was compared between groups using Kruskal-Wallis H test. Mean values for each experiment were compared between groups using a one-way analysis of variance and LSD-t test.Spearman rank analysis was used to evaluate the correlation between the haze grading and the expression of TUNEL positive cells and α-SMA.
The corneas of seventy-two eyes reepithelialized in 6 days after operation. The average epithelium repair time of the AE group was (4.12 ± 0.62) d, the dexamethasone group was (5.25 ± 0.78) d, and the excipient group was (4.96 ± 0.73) d. The progression of reepithelialization was significantly faster in the AE group than the other two groups (F = 14.144, P < 0.01). The haze appeared in the first week after the PRK in all three groups, increased after 3-4 weeks, and relieved after 8 weeks. The degree of haze was significantly lower in the AE group than the other two groups in the first week (Vs. dexamethasone group, H = 3.995, P < 0.05; vs. excipient group, H = 12.77, P < 0.01), in the 4th week (Vs. dexamethasone group, H = 4.468, P < 0.05;vs. excipient group, H = 9.003, P < 0.01), and 8th week (Vs dexamethasone group, H = 4.397, P < 0.05;vs. excipient group, H = 5.744, P < 0.05) after PRK. The TUNEL-positive cells appeared in the central anterior stroma at the first week after surgery. And the number of TUNEL-positive cells in the AE group was (2.2500 ± 0.3750) cells/HP, the dexamethasone group was (4.5000 ± 0.7500) cells/HP, and the excipient group was (7.1250 ± 0.9063) cells/HP. The number of TUNEL-positive cells in AE group was less than those in the other two groups (Vs. dexamethasone group, t = 4.26, P < 0.01; vs. excipient group, t = 8.13, P < 0.01). The TUNEL-positive cells were only found in the excipient group (2.8750 ± 0.6563)/HP in 4th week after operation.It was significantly different between the dexamethasone group and the excipient group (t = 9.01, P < 0.01). There were no significant TUNEL-positive cells in 8th weeks in all three groups.α-SMA-positive cells started to appear apparently at the first week after surgery in the dexamethasone and excipient groups, and the peaks appeared at the 4th week after treatments, and there were still a lot of α-SMA-positive cells in corneal stroma at the 8th week after operation in both groups.On the contrary, there were no significant α-SMA-positive cells in the AE group all the time after surgery. The statistical significant difference can be found between the AE group vs. the dexamethasone and excipient groups in the first week (t = 28.62, 36.55;P < 0.01), in the 4th week (t = 30.40, 35.96; P < 0.01), and in the 8th week (t = 34.02, 38.32; P < 0.01).Spearman rank analysis demonstrated that the formation of haze was proportional to the expression of TUNEL positive cells (r = 0.881, P < 0.01) and α-SMA (r = 0.710, P < 0.01).
Amniotic extraction can reduce the formation of haze, which was more effective than 0.1% dexamethasone.It might release certain factors which were transported into corneal matrix, then affected the healing of epithelial cell by interacting with the corneal cell factors, reducing the cell apoptosis, corneal wound healing response and rebuilding the corneal matrix with less myofibroblast, collagen and scar and finally reduce the formation of haze.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 01/2014; 50(1):42-50.
[Show abstract][Hide abstract] ABSTRACT: To establish normal noninvasive tear film breakup time (NI-BUT) values in the Chinese population and investigate age-related changes in NI-BUT using a newly developed Keratograph.
Forty normal volunteers with a mean age of 32.8 ± 16.7 years were recruited for this study. Clinical and demographic data, including age, gender, fluorescein tear film breakup time (FBUT), and Schirmer I test values were collected from the subjects. Noninvasive tear film breakup time was measured using a new method based on a corneal topographer equipped with a modified scan software. The correlations between the NI-BUT, age, and gender were determined.
In total, a significant difference between the NI-BUT and the FBUT was found (4.9 ± 2.4 seconds vs. 9.0 ± 3.0 seconds; p < 0.001). No statistically significant difference in the NI-BUT was observed between the male and female subjects (5.5 ± 2.0 seconds vs. 4.5 ± 2.5 seconds; p = 0.137). In addition, no significant correlation was detected between the NI-BUT and age (0.143, p = 0.321).
The NI-BUT values found in this study are much lower than those of previous reports. Our results show no significant differences in tear film stability with age. The tear physiology of the Chinese population may not be the same as in Western populations.
Optometry and vision science: official publication of the American Academy of Optometry 11/2013; · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: Endothelial progenitor cells (EPC) have been shown to participate in ischemia-induced retinal neovascularization (NV). Over-activation of Wnt signaling plays a pathogenic role in ischemia-induced retinal NV. The purpose of this study is to determine whether Wnt signaling regulates EPC release. Methods: Oxygen-induced retinopathy (OIR) was used as a model of retinal NV and Wnt pathway activation. EPC, marked as c-Kit+/Tie-2+ cells in the peripheral blood and bone marrow, were quantified using flow cytometry following immunolabeling. Wnt signaling activity was evaluated by measuring non-phosphorylated β-catenin levels and X-gal staining in the Wnt reporter mice (Bat-gal mice). Results: c-Kit+/Tie-2+ cells were significantly increased in both of the peripheral blood and bone marrow of mice with OIR, compared to non-OIR mice. Over-expression of kallistatin, an endogenous inhibitor of the Wnt pathway, in kallistatin transgenic (kallistatin-TG) mice with OIR attenuated the increases of c-Kit+/Tie-2+ cells in the peripheral blood and bone marrow, compared to WT mice with OIR. When the Bat-gal mice were crossed with kallistatin-TG mice, kallistatin over-expression suppressed the OIR-induced increases of X-gal positive cells in the retinas and bone marrow, suggesting inhibition of Wnt signaling in these tissues. Furthermore, intraperitoneal injection of LiCl, a Wnt signaling activator, increased c-Kit+/Tie-2+ cells in the peripheral blood of normal mice. Consistently, LiCl activated Wnt signaling in both of the retina and bone marrow cells in Bat-gal mice. Conclusions: Wnt signaling plays an important role in EPC release during retinal NV in OIR.
[Show abstract][Hide abstract] ABSTRACT: To investigate the effect of benzalkonium chloride (BAK) on corneal nerves.
Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9.
The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes.
The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE. To develop a mouse model of limbal stem cell deficiency (LSCD) by topical administration of benzalkonium chloride (BAC). METHODS. BAC solutions (0% to 0.5%) were applied to the mouse ocular surface for 4 weeks. Corneal neovascularization, inflammation, and epithelial status were observed under slitlamp microscope. The eyeball and ocular surface tissues were collected at 4 weeks and 12 weeks, and labeled with a series of antibodies. Limbal structure was evaluated by light and transmission electron microscopy (TEM). Corneal impression cytology was performed at 12 weeks and labled with periodic acid Schiff (PAS) reagents. RESULTS. 0.5% BAC four times per day for 28 days successfully induced the typical manifestations of LSCD, including corneal neovascularization, severe inflammation in the stroma, and diffuse epithelial defect (P<0.001). K19 and K13 were positive on the corneal surface. P63 and ABCG2 expression were abolished in the limbal epithelium. β-catenin was negative in the basal layer. TEM revealed the irregular basement membrane and the loss of stem cell-specific ultrastructure in the limbal basal epithelium. In 0.5% BAC group, goblet cells could not be observed on day 28 but emerged after the cessation of BAC, and remained over the cornea after eight weeks. K13-positive cells were still present over the cornea with the loss of K12. CONCLUSIONS. Topical administration of BAC at high concentration and frequency in mouse induces ocular surface changes resembling that of LSCD in humans, representing a novel model of LSCD.
[Show abstract][Hide abstract] ABSTRACT: Kallistatin is a member of the serine proteinase inhibitor superfamily. Kallistatin levels have been shown to be decreased in the vitreous, while increased in the circulation of patients with diabetic retinopathy (DR). Over-activation of the Wnt pathway is known to play pathogenic roles in DR. To investigate the role of kallistatin in DR and in Wnt pathway activation, we generated kallistatin transgenic (kallistatin-TG) mice over-expressing kallistatin in multiple tissues including the retina. In the oxygen-induced retinopathy (OIR) model, kallistatin over-expression attenuated ischemia-induced retinal neovascularization. In diabetic kallistatin-TG mice, kallistatin over-expression ameliorated retinal vascular leakage, leukostasis and over-expression of VEGF and ICAM-1. Furthermore, kallistatin over-expression also suppressed Wnt pathway activation in the retinas of the OIR and diabetic models. In diabetic Wnt reporter (BAT-gal) mice, kallistatin over-expression suppressed retinal Wnt reporter activity. In cultured retinal cells, kallistatin blocked Wnt pathway activation induced by high glucose and by Wnt ligand. Co-precipitation and ligand binding assays both showed that kallistatin binds to a Wnt co-receptor LRP6 with high affinity (Kd=4.5 nM). These observations suggest that kallistatin is an endogenous antagonist of LRP6 and inhibitor of Wnt signaling. The blockade of Wnt signaling may represent a mechanism for its anti-angiogenic and anti-neuroinflammatory effects.