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author:("Xu, qianjiang")
1.  Assessment of Corneal Epithelial Thickness in Dry Eye Patients 
To investigate the features of corneal epithelial thickness topography with Fourier-domain optical coherence tomography (OCT) in dry eye patients.
In this cross-sectional study, 100 symptomatic dry eye patients and 35 normal subjects were enrolled. All participants answered the ocular surface disease index questionnaire and were subjected to OCT, corneal fluorescein staining, tear breakup time, Schirmer 1 test without anesthetic (S1t), and meibomian morphology. Several epithelium statistics for each eye, including central, superior, inferior, minimum, maximum, minimum – maximum, and map standard deviation, were averaged. Correlations of epithelial thickness with the symptoms of dry eye were calculated.
The mean (±SD) central, superior, and inferior corneal epithelial thickness was 53.57 (±3.31) μm, 52.00 (±3.39) μm, and 53.03 (±3.67) μm in normal eyes and 52.71 (±2.83) μm, 50.58 (±3.44) μm, and 52.53 (±3.36) μm in dry eyes, respectively. The superior corneal epithelium was thinner in dry eye patients compared with normal subjects (p=0.037),whereas central and inferior epithelium were not statistically different. In the dry eye group, patients with higher severity grades had thinner superior (p = 0.017) and minimum (p < 0.001) epithelial thickness, more wide range (p = 0.032), and greater deviation (p = 0.003). The average central epithelial thickness had no correlation with tear breakup time, S1t, or the severity of meibomian glands, whereas average superior epithelial thickness positively correlated with S1t (r = 0.238, p = 0.017).
Fourier-domain OCT demonstrated that the thickness map of the dry eye corneal epithelium was thinner than normal eyes in the superior region. In more severe dry eye disease patients, the superior and minimum epithelium was much thinner, with a greater range of map standard deviation.
PMCID: PMC4302058  PMID: 25279779
optical coherence tomography; dry eye syndromes; epithelium; corneal; corneal pachymetry; tear film
2.  A Multi-Center, Cross-Sectional Study on the Burden of Infectious Keratitis in China 
PLoS ONE  2014;9(12):e113843.
To understand the prevalence and demographic characteristics of infectious keratitis and infectious corneal blindness.
A multi-center, population-based cross-sectional study was conducted from January 1 to August 31, 2010. A total of 191,242 individuals of all age groups from 10 geographically representative provinces were sampled using stratified, multi-stage, random and systematic sampling procedures. A majority, 168,673 (88.2%), of those sampled participated in the study. The examination protocol included a structured interview, visual acuity testing, an external eye examination, and an anterior segment examination using a slit lamp. The causes and sequelae of corneal disease were identified using uniform customized protocols. Blindness in one eye caused by infectious keratitis was defined as infectious corneal blindness.
The prevalence of past and active infectious keratitis was 0.192% (95% confidence interval [CI], 0.171–0.213%), and the prevalence of viral, bacterial, and fungal keratitis was 0.11%, 0.075%, and 0.007%, respectively. There were 138 cases of infectious corneal blindness in at least one eye in the study population (prevalence of 0.082% [95%CI, 0.068%–0.095%]). Statistical analysis suggested that ocular trauma, alcoholic consumption, low socioeconomic levels, advanced age, and poor education were risk factors for infectious corneal blindness.
Infectious keratitis is the leading cause of corneal blindness in China. Eye care strategies should focus on the prevention and rehabilitation of infectious corneal blindness.
PMCID: PMC4250054  PMID: 25438169
3.  Impact of Conjunctivochalasis on Visual Quality of Life: A Community Population Survey 
PLoS ONE  2014;9(10):e110821.
Conjunctivochalasis (Cch) is a very common ocular disorder, which can cause an unstable tear film and ocular discomfort. The study of vision-related quality of life (VR-QoL) in a community population with Cch can provide a better understanding of the impact of Cch on common people than objective clinical examinations alone. This cross-sectional comparative study enrolled 360 participants ≥40 years old living in Sanle Community, Shanghai. In the study, 198 subjects were diagnosed with Cch and 86 with dry eye syndrome (DES) without Cch. The remaining 76 subjects were normal controls. Socio-demographical data were collected, and Cch and related ocular symptoms and signs were evaluated. In addition, all participants were required to complete the Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Ocular Surface Disease Index Questionnaire (OSDI). Main outcome measures include the comparison on the OSDI score and VFQ-25 score among the subgroups, and the correlation of these scores with the socio-demographical and clinical data. The results revealed that subjects with Cch had significantly decreased tear film stability even compared with those with DES (P = 0.001). The participants with either Cch or DES reported significantly higher OSDI scores and lower VFQ-25 composite scores than the normal controls (P<0.001 and 0.007 respectively). Further comparisons among the subgroups of Cch revealed that the following factors were associated with higher OSDI scores and lower VFQ-25 composite scores: nasal-side Cch, chalasis folds higher than tear meniscus height, punctal occlusion, or increased extent of chalasis on digital pressure. In conclusion, Cch was associated with an adverse impact on VR-QoL in a community population, and the impairment in VR-QoL had a significant correlation with disease severity and tear film abnormalities.
PMCID: PMC4203838  PMID: 25330252
4.  An unusual case of Acanthamoeba Polyphaga and Pseudomonas Aeruginosa keratitis 
Diagnostic Pathology  2014;9:105.
Virtual Slides
The virtual slide(s) for this article can be found here:
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.
PMCID: PMC4051961  PMID: 24894486
Contact lens; Acanthamoeba species; Pseudomonas aeruginosa
5.  Impact of Dry Eye Syndrome on Vision-Related Quality of Life in a Non-Clinic-Based General Population 
BMC Ophthalmology  2012;12:22.
Dry eye syndrome (DES) is a common ocular disorder occurring in general population. The purpose of this study is to evaluate the impact of DES on vision-related quality of life (QoL) in a non-clinic-based general population.
This population-based cross-sectional study enrolled subjects older than 40 years, who took part in an epidemiological study on dry eye in Sanle Community, Shanghai. Apart from the collection of sociodemographics, dry eye symptoms, and other clinical data, a Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was administered to all subjects. Comparisons of the NEI VFQ-25 subscale item scores and composite score were made among subgroups divided according to the presence of dry eye symptoms or signs. Multivariate regression analysis was performed to investigate the relationship between the clinical variables and the VFQ-25 composite score.
A total of 229 participants were enrolled in the study, with an average age of (60.7 ±10.1) years old. Majority of these participants were female (59.8 %, 137/229). The total DES symptom scores (TDSS) in subjects either with definite DES or only with dry eye symptoms were significantly higher (F = 60.331, P < 0.001). The values of tear break-up time (TBUT) and Schirmer test were significantly lower in participants with DES and those with dry eye signs only (F = 55.158 and 40.778, P < 0.001). The composite score of the NEI VFQ-25 was significantly lower in subjects with DES (F = 4.901, P = 0.003). Moreover, the subscale scores of ocular pain and mental health were significantly lower in those with either DES or dry eye symptoms only (F = 10.962 and 7.362 respectively, both P < 0.001). The multiple regression analysis showed that the TDSS had a significant negative correlation with the VFQ-25 composite score as well as with the subscale score for ocular pain and mental health, even after the adjustment of all other factors (all P < 0.01).
The symptoms of dry eye are associated with an adverse impact on vision-related QoL in non-clinic-based general population, which is mainly represented as more ocular pain and discomfort, and impaired mental health as well. Apart from clinical examination, it is also important to refer to subjective symptoms and QoL scores when assessing the severity of DES.
PMCID: PMC3437197  PMID: 22799274
Dry eye syndrome; NEI VFQ-25; Visual quality of life
6.  Analysis of medical expenditure and socio-economic status in patients with ocular chemical burns in East China: a retrospective study 
BMC Public Health  2012;12:409.
Little has been known regarding the relationship between ocular chemical injury and victims’ medical expenditure, income loss and socio-economic status changes. So we conduct this retrospective cross-sectional study in patients with ocular chemical burns in East China.
Fifty-six patients were enrolled and required to complete a self-report questionnaire consisting of the following contents: entire expenditure on medical treatment; the victims’ personal and household per capita income, and income loss caused by the injury; and the changes of socioeconomic status as well.
The median expense of medical treatment was CNY 40,000 (approximately US$5,900). The medical expenditure rose significantly with increased injury severity, prolonged hospital stay, and increased frequency of surgery. More than half victims (51.8 %, 29/56) paid all or the majority of medical expense by themselves. The expense of only 5 victims was mainly paid by medical insurance, accounting for less than ten percent (8.9 %, 5/56). The victims’ personal and household per capita income both decreased significantly after the injury, with the median reduction being CNY 24,000 and CNY 7,800 (approximately US$3600 and US$1200) per year respectively. The reduction amplitude of personal and household per capita income rose with increased injury severity and prolonged time of care required. The injury caused emotional depression or anxiety in 76.8 % (43/56) victims, and the relationship with their relatives got worse in 51.9 % (29/56) patients. Moreover, only 21.4 % (12/56) patients felt that the whole society gave them care and concern after the injury, whereas 46.4 % (26/56) and 28.6 % (16/56) felt indifference or discrimination from society as a whole (X2 = 16.916, P = 0.028).
The medical expense was a huge economic burden to most victims of ocular chemical burns, and personal and household per capita income of the victims decreased significantly after injury, both of which had a close relationship with the injury severity. Formal legislation was urgently needed to compel the employer to purchase injury or medical insurance and provide more compulsory protection to the population working in high risk occupations. In addition, psychological counseling and instruction shouldn’t be neglected in the aid and treatment of victims.
PMCID: PMC3408343  PMID: 22672729
Burns, Chemical; Medical expenditure; Socio-economic status; China
7.  Heightened expression of MICA enhances the cytotoxicity of NK cells or CD8+T cells to human corneal epithelium in vitro 
BMC Ophthalmology  2012;12:6.
Major-histocompatibility-complex class I-related chain A (MICA) antigens are the ligands of NKG2D, which is an activating or coactivating receptor expressed on human NK cells and CD8+T cells. We sought to determine whether MICA expression in human corneal epithelium (HCE) could affect the cytotoxicity mediated by NK cells or CD8+T cells.
Cell cultures of HCE were harvested from human donor eyes. Flow cytometric analysis and ELISA was performed to determine the levels of MICA expression on HCE. Then, HCE was transfected with a lentivirus vector expressing MICA and GFP. Flow cytometric analysis, RT-PCR, western blot and ELISA were performed to check the levels of MICA expression. For cytotoxicity testing, allogeneic NK cells and CD8+T cells were isolated from peripheral blood mononuclear cells of healthy volunteers by magnetic cell sorting. The cytolytic activity of NK cells and CD8+T cells was assessed against MICA-transfected HCE (NK cells: E:T ratio = 3:1; CD8+T cells: E:T ratio = 10:1) using the nonradioactive cytotoxicity detection kit lactate deshydrogenase.
Surface expression of MICA on corneal epithelium was identified at a low level. A cell line of stable human MICA-transfected corneal epithelium was successfully established. Heightened expression of MICA on HCE was found to promote the cytotoxicity mediated by NK cells or CD8+T cells, which could be blocked by an anti-MICA antibody.
MICA molecules may contribute to cytotoxic responses mediated by activated immune effector cells in corneal epithelium immunity.
PMCID: PMC3733519  PMID: 22475346
8.  NGF promotes cell cycle progression by regulating D-type cyclins via PI3K/Akt and MAPK/Erk activation in human corneal epithelial cells 
Molecular Vision  2012;18:758-764.
Nerve growth factor (NGF) plays an important role in promoting the healing of corneal wounds. However, the molecular mechanism by which NGF functions is unknown. We investigated the possible effects of NGF on phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) pathways and cell growth in human corneal epithelial cells (HCECs).
We examined the effect of NGF on cell cycle and proliferation in HCECs by flow cytometry and cell proliferation assay, respectively. The levels of D-type cyclins in NGF-treated HCECs were determined by western blot. The tyrosine kinase A (TrkA), PI3K/Akt and MAPK/Erk pathways were then checked in cells stimulated with NGF for different time periods or cells undergoing a dose-dependent treatment. Furthermore, HCECs were treated with pathway inhibitors, LY294002 or PD98059, to confirm NGF-induced activations.
We found that NGF had a positive effect on the growth of HCECs, and D-type cyclins, and it was correlated with the percentage of the G1 to S progression. We also observed a time-dependent and dose-dependent effect of NGF on the PI3K/Akt and MAPK/Erk pathways. Furthermore, NGF affected cell cycle progression of HCECs by regulating cyclin D through Akt and Erk activation upon treatment with the pathway inhibitors, LY294002 for Akt or PD98059 for Erk pathways.
NGF stimulation could promote cell proliferation and cell cycle progression of HCECs by activation of cyclin D via the PI3K/Akt and MAPK/Erk signaling pathways.
PMCID: PMC3324366  PMID: 22509106
9.  RNA interference as a gene silencing therapy for mutant MYOC protein in primary open angle glaucoma 
Diagnostic Pathology  2009;4:46.
Primary open-angle glaucoma (POAG) is the most common form of glaucoma which is an irreversible blind leading disease and lacks effective remedies. In recent years, POAG has been linked to the gene MYOC encoding myocilin that has been identified to harbor causal mutations. A variety of studies show that the mutant myocilin acts by gain of function. The mutant MYOC protein induces endoplasmic reticulum (ER) stress and the resultant unfolded protein response (UPR) induces apoptosis in the trabecular meshwork cells, which then leads to an increase in resistance to aqueous humor outflow, elevated intraocular pressure (IOP), and, ultimately, glaucoma. Culturing human trabecular meshwork (HTM) cells at a condition facilitating protein folding promotes secretion of mutant myocilin, normalizes cell morphology and reverses cell lethality.
Presentation of the Hypothesis
We speculate that a complete elimination of mutant myocilin expression in trabecular meshwork cells is safe and that gives the possibility of avoiding the POAG phenotype.
Testing the Hypothesis
We propose RNA interference (RNAi) as a gene silencing therapy to eliminate the mutant myocilin proteins in the trabecular meshwork cells, either in a mutation-dependent or mutation-independent way due to the different engineering of the small interfering (si) RNA.
Implications of the Hypothesis
The RNAi strategy can reverse the pathological process of trabecular meshwork cells and thus treat the POAG caused by myocilin gene mutation. This strategy can also be applicable to many protein-misfolding diseases caused by gain-of-function mutant proteins.
PMCID: PMC2801471  PMID: 20015381
10.  Histology of corneal wound healing after deep lamellar endothelial keratoplasty 
Deep lamellar endothelial keratoplasty (DLEK) has become an alternative procedure for bullous keratopathy. Herein, the histopathological characteristics of corneal wound healing after DLEK were reported. A 71-year-old man suffering from left psuedophakia bullous keratopathy received small incision DLEK. Twenty months later, another penetrating keratoplasty (PK) was performed because of the graft failure. The histopathology of the corneal button removed during PK demonstrated the regularity of stromal fiber alignment at the graft interface. Fibrotic repair was limited to the peripheral margins.
PMCID: PMC2698693  PMID: 19668409
Deep lamellar endothelial keratoplasty; DLEK; bullous keratopathy; penetrating keratoplasty

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