[Show abstract][Hide abstract] ABSTRACT: Each year, over 8,000 corneal transplantation surgeries are performed in China. Unlike developed countries, which have established standard requirements for operative experience for corneal specialists, little information exists on surgical training for keratoplasty in China. The aim of this study was to assess the keratoplasty experience of Chinese corneal specialists and to characterize their surgical patterns.
One hundred and twenty-one corneal specialists in 16 provinces (65 cities) in China were invited to complete an anonymous survey at the 2014 Chinese Corneal Society annual meeting, which consisted of questions with single or multiple-choice answers. Demographics, the number and type of keratoplasties performed, and the perceived limiting factors for performing keratoplasties were analyzed.
An overwhelming 89% response rate was achieved. Of the 108 respondents, 76% worked in tertiary centers, and only 23% held a medical doctorate degree. Furthermore, 69% of the participants had received corneal fellowship training of less than one year. Only 71% were capable of keratoplasties. Among those doing keratoplasty, 68% performed less than 50 keratoplasties each year. Of the same group of keratoplasty surgeons, 88% of corneal specialists capable of keratoplasties had performed penetrating keratoplasties, 87% had performed lamellar keratoplasties, 12% had performed deep anterior lamellar keratoplasties, and 5% had performed Descemet's stripping endothelial keratoplasties. When questioned on the reasons for the low number of keratoplasties performed in China, the respondents deemed the following factors most important: lack of surgical training (71%), a shortage of donor supply (52%), and a lack of curricula (42%). A multivariate logistic regression analysis showed that corneal transplantation capabilities are significantly associated with responders' education levels and training time.
Keratoplasty surgery experience is suboptimal for Chinese corneal specialists. Penetrating and lamellar keratoplasties are the preferred surgical patterns. Our findings raise concerns about the adequacy of keratoplasty training in China.
PLoS ONE 07/2015; 10(7):e0132268. DOI:10.1371/journal.pone.0132268 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A variety of pluripotency reprogramming frequencies from different somatic cells has been observed, indicating cell origin is a critical contributor for efficiency of pluripotency reprogramming. Identifying the cell sources for efficient induced pluripotent stem cells (iPSCs) generation, and defining its advantages or disadvantages on reprogramming, is therefore important. Human ocular tissue-derived conjunctival epithelial cells (OECs) exhibited endogenous expression of reprogramming factors OCT4A (the specific OCT 4 isoform on pluripotency reprogramming) and SOX2. We therefore determined whether OECs could be used for high efficiency of iPSCs generation. We compared the endogenous expression levels of four pluripotency factors and the pluripotency reprograming efficiency of human OECs with that of ocular stromal cells (OSCs). Real-time PCR, microarray analysis, Western blotting and immunostaining assays were employed to compare OECiPSCs with OSCiPSCs on molecular bases of reprogramming efficiency and preferred lineage-differentiation potential. Using the traditional KMOS (KLF4, C-MYC, OCT4 and SOX2) reprogramming protocol, we confirmed that OECs, endogenously expressing reprogramming factors OCT4A and SOX2, yield very high efficiency of iPSCs generation (~1.5%). Furthermore, higher efficiency of retinal pigmented epithelial differentiation (RPE cells) was observed in OECiPSCs compared to OSCiPSCs or skin fibroblast iMR90iPSCs. The findings in this study suggest that conjunctival-derived epithelial (OECs) cells can be easier converted to iPSCs than conjunctival-derived stromal cells (OSCs). This cell type may also have advantages in retinal pigmented epithelial differentiation.
PLoS ONE 07/2015; 10(7):e0131288. DOI:10.1371/journal.pone.0131288 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Netrins are secreted molecules involved in axon guidance and angiogenesis. However, the role of netrins in the vasculature remains unclear. Netrin-4 and netrin-1 have been found to be either pro- or antiangiogenic factors. Previously, we found that netrin-1 acts as an anti-angiogenic factor in rats by inhibiting alkali burn-induced corneal neovascularization. Here, we further investigate the effects of netrin-4, another member of the same netrin family, on neovascularization in vitro and in vivo. We found that netrin-4 functions similarly as netrin-1 in angiogenesis. In vitro angiogenesis assay shows that netrin-4 affected human umbilical vein endothelial cell (HUVEC) tube formation, viability and proliferation, apoptosis, migration, and invasion in a dose-dependent manner. Netrin-4 was topically applied in vivo to alkali-burned rat corneas on day 0 (immediately after injury) and/or day 10 post-injury. Netrin-4 subsequently suppressed and reversed corneal neovascularization. Netrin-4 inhibited corneal epithelial and stromal cell apoptosis, inhibited vascular endothelial growth factor (VEGF), but promoted pigment epithelium-derived factor (PEDF) expression, decreased NK-KB p65 expression, and inhibits neutrophil and macrophage infiltration. These results indicate that netrin-4 shed new light on its potential roles in treatmenting for angiogenic diseases that affect the ocular surface, as well as other tissues.
PLoS ONE 04/2015; 10(4):e0122951. DOI:10.1371/journal.pone.0122951 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare the postoperative measurements of intraocular pressure (IOP) using the Corvis ST Tonometer (CST), ocular response analyzer (ORA), and Goldmann applanation tonometry (GAT) in eyes undergoing laser in situ keratomileusis (LASIK), as well as to analyze the relationship between the corneal biomechanical parameters of the CST and the ORA.
Fifty participants who had undergone LASIK to treat myopia in the previous 3 months were enrolled. Postoperative IOP measurements of these participants were obtained using the CST, ORA (corneal-compensated IOP [IOPcc], Goldmann-correlated IOP [IOPg]), and GAT. Device agreement was calculated by Bland-Altman analysis. The metrics of corneal biomechanical properties were recorded using the ORA and the CST. Corneal biomechanical parameters were compared.
The Bland-Altman analysis revealed a significant bias between CST and GAT, between CST and IOPcc, and between CST and IOPg of 3.4, 1.0, and 3.8, mm Hg, respectively, with 95% limits of agreement of -0.7 to 7.5 mm Hg, -2.1 to 4.2 mm Hg, and -0.4 to 8.0 mm Hg. The ORA-derived IOP measurements, CST-derived IOP, and GAT IOP values showed good correlation with each other. The CST IOP and IOPcc were higher than the GAT IOP (all p < 0.05), whereas IOPg did not differ from the GAT IOP readings. Ocular response analyzer-derived corneal biomechanical parameters (corneal hysteresis and the corneal resistance factor) showed significant correlations with CST-derived parameters, including the maximum deformation amplitude at the corneal apex and the time from start until the first applanation.
The CST offers an alternative method for measuring postoperative IOP in LASIK patients, and it appears to obtain higher IOP values than other tonometry techniques. The technique may facilitate the investigation of corneal biomechanical property changes in LASIK-treated eyes.
Optometry and vision science: official publication of the American Academy of Optometry 03/2015; 92(5). DOI:10.1097/OPX.0000000000000575 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Periostin is a non-structural matricellular protein. Little is known about periostin in human limbal stem cells (LSCs). This study was to explore the unique expression pattern and functional role of periostin in maintaining the properties of human LSCs. Fresh donor corneal tissues were used to make cryosections for evaluation of periostin expression on ex vivo tissues. Primary human limbal epithelial cells (HLECs) were generated from limbal explant culture. In vitro culture models for proliferation and epithelial regeneration were performed to explore functional role of periostin in LSCs. The mRNA expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), and the protein production and localization were detected by immunofluorescent staining and Western blot analysis. Periostin protein was found to be exclusively immunolocalized in the basal layer of human limbal epithelium. Periostin localization was well matched with nuclear factor p63, but not with corneal epithelial differentiation marker Keratin 3. Periostin transcripts was also highly expressed in limbal than corneal epithelium. In primary HLECs, periostin expression at mRNA and protein levels was significantly higher in 50% and 70% confluent cultures at exponential growth stage than in 100% confluent cultures at slow growth or quiescent condition. This expression pattern was similar to other stem/progenitor cell markers (p63, integrin β1 and TCF4). Periostin expression at transcripts, protein and immunoreactivity levels increased significantly during epithelial regeneration in wound healing process, especially in 16-24 hours at wound edge, which was accompanied by similar upregulation and activation of p63, integrin β1 and TCF4. Our findings demonstrated that periostin is exclusively produced by limbal basal epithelium and co-localized with p63, where limbal stem cells reside. Periostin promotes HLEC proliferation and regeneration with accompanied activation of stem/progenitor cell markers p63, integrin β1 and TCF4, suggesting its novel role in maintaining the phenotype and functional properties of LSC.
PLoS ONE 02/2015; 10(2):e0117139. DOI:10.1371/journal.pone.0117139 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls. The HLA-DRB1*0803 is the allele that shows the strongest association with pSS in Chinese population (OR = 3.0, P = 2.4 × 10−4). Furthermore, amino acid variations within the binding pocket P7 and P9 are associated with the susceptibility to pSS. An interaction between two residues within P7, β47 and β67, is associated with pSS. Structural modeling studies demonstrated that the electrostatics of peptide binding pocket 9 are opposite in pSS-susceptible and -protective HLA-DRB1 alleles. In conclusion, our results suggest that structural heterogeneity of the HLA-DRB1 peptide binding pocket P7 and P9 might play a role in the pathogenesis of pSS.
Journal of Autoimmunity 01/2015; 57. DOI:10.1016/j.jaut.2014.11.006 · 7.02 Impact Factor
[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: Purpose: Using anterior chamber optical coherence tomography to evaluate changes in angle anatomy in patients with primary angle-closure glaucoma (PACG) before and after trabeculectomy. Methods: This is a prospective observational study in 38 eyes of 38 patients with PACG, who underwent trabeculectomy. We used customized software to analyze optical coherence tomography images (Visante) of all participants before and after the surgical treatment. Multivariate linear regression analysis was performed for predictors of percentage change in mean angle parameters, including scleral spur angle, angle opening distance, angle recess area, and trabecular-iris surface area. The main outcome measures were changes in angle parameters and their relationship with age, sex, refraction, MD, visual outcomes, central corneal thickness, axial length of eye, number of glaucoma bottles, baseline intraocular pressure (IOP), and percentage changes in IOP ([DELTA]IOP). Results: There was a significant increase in all angle parameters at the follow-up examination compared with the baseline value (all P<0.001). After multivariate analysis, the only variable related to changes in all angle parameters was [DELTA]IOP. Conclusions: Trabeculectomy results in a significant increase in the angle width in PACG. The increase in angle parameters was significantly related to the IOP changes.
Journal of Glaucoma 10/2014; Publish Ahead of Print. DOI:10.1097/IJG.0000000000000153 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose: To map the corneal epithelial thickness in vivo with Fourier-domain optical coherence tomography in long-term soft contact lens (SCL) wearers. Methods: This is a cross-sectional observational study. Forty eyes from 40 normal subjects who had never worn SCL and 40 eyes from 40 SCL wearers who had worn lenses for more than 2 years were enrolled. Corneal epithelium over the entire cornea was topographically imaged using a novel optical coherence tomography system. An epithelial thickness map was automatically generated. Epithelial thicknesses of the central 2-mm, paracentral 2- to 5-mm (P1), and midperipheral 5- to 6-mm (P2) zones were obtained. In addition, the epithelial map variability in P1 and P2 zones, including maximum − minimum (MAX − MIN), map SD, and coefficient of variation (CV), was measured and analyzed. Results: The average epithelial thickness of the central, P1, and P2 zones was 54.4 ± 1.1 μm, 53.2 ± 2.2 μm, and 52.3 ± 2.0 μm, respectively, in normal eyes and 49.2 ± 1.9 μm, 48.8 ± 2.2 μm, and 48.7 ± 2.8 μm, respectively, in eyes wearing SCL. Compared with normal control subjects, eyes with long-term SCL had significantly thinner epithelial thickness in all three zones (p < 0.05). However, there was no difference in MAX − MIN, SD, and CV of P1 and P2 zones between two groups. In both groups, there was significant difference in the epithelial thickness among different sectors in the paracentral and midperipheral zones. Conclusions: There is a decrease in epithelial thickness in subjects who wear SCL long term. Clinicians should take note of the nonuniformity of the paracentral and midperipheral corneal epithelium thicknesses. This method may be useful for detecting early changes in corneal epithelial thickness caused by long-term SCL wear.
Optometry and vision science: official publication of the American Academy of Optometry 10/2014; 91(12). DOI:10.1097/OPX.0000000000000410 · 2.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
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.
Thirty-six adult New Zealand albino rabbits were randomly divided into three groups. BAK at 0.01%, 0.05%, and 0.1% was applied twice daily to one eye of each of the rabbits in one of the three groups for seven days. The contralateral untreated eyes were used as controls. Corneal endothelial morphological features were observed by in vivo confocal microscopy (IVCM). Immunofluorescent staining resolved changes in gap junction integrity and localization. Western blot analysis and RT-PCR evaluated changes in levels of connexin43 (Cx43) and tight junction zonula occludens-1 (ZO-1) gene and protein expression, respectively. Cx43 and ZO-1 physical interaction was detected by immunoprecipitation (IP). Primary rabbit corneal endothelial cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing BAK for 24 hours. The scrape-loading dye transfer technique (SLDT) was used to assess GJIC activity.
Topical administration of BAK (0.05%, 0.1%) dose dependently disrupted corneal endothelial cell morphology, altered Cx43 and ZO-1 distribution and reduced Cx43 expression. BAK also markedly induced increases in Cx43 phosphorylation status concomitant with decreases in the Cx43-ZO-1 protein-protein interaction. These changes were associated with marked declines in GJIC activity.
The dose dependent declines in rabbit corneal endothelial GJIC activity induced by BAK are associated with less Cx43-ZO-1 interaction possibly arising from increases in Cx43 phosphorylation and declines in its protein expression. These novel changes provide additional evidence that BAK containing eyedrop preparations should be used with caution to avoid declines in corneal transparency resulting from losses in GJIC activity and endothelial function.
PLoS ONE 10/2014; 9(10):e109708. DOI:10.1371/journal.pone.0109708 · 3.23 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 10/2014; 9(10):e108859. DOI:10.1371/journal.pone.0108859 · 3.23 Impact Factor
[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.
Current Eye Research 09/2014; 40(8):1-8. DOI:10.3109/02713683.2014.959608 · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased tear osmolarity is one of the core mechanisms of dry eye and has been considered as an important diagnostic criterion, if not"gold standard", of dry eye. However, recent studies showed the limitations of tear osmolarity measurement not only in the diagnosis, but also in the therapeutic efficacy evaluation of dry eye. The clinical significance of tear osmolarity measurement has become a hot topic of argument. Herein, we review the publications on this topic and try to find the underlying causes of such argument.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 09/2014; 50(9):650-7.
[Show abstract][Hide abstract] ABSTRACT: Translational medicine emphasizes the application of the results of basic research to clinical practice and the solution of clinical issues through basic research. It is very important for the development direction of the medical field. Over the past decade, the translational medicine research in ocular surface disease has drawn international attention and developed rapidly. This field in China has made great progress, but overall there are still some gaps with the international advanced level. We need to establish the concept and the platform of translational research, explore scientific and effective methods, and create a whole chain to enhance our ocular research. It also requires research institutions and government departments to give full support. Finally, we need to explore a suitable way for the development of Chinese translational medical research.
[Zhonghua yan ke za zhi] Chinese journal of ophthalmology 09/2014; 50(9):646-9.
[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.