Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data.

OBJECTIVE: Genotype imputation is a commonly used technique that infers un-typed variants into a study's genotype data, allowing better identification of causal variants in disease studies. However, due to overrepresentation of Caucasian studies, there's a lack of understanding of genetic basis of health-outcomes in other ethnic populations. Therefore, facilitating imputation of missing key-predictor-variants that can potentially improve a risk health-outcome prediction model, specifically for Asian ancestry, is of utmost relevance. METHODS: We aimed to construct an imputation and analysis web-platform, that primarily facilitates, but is not limited to genotype imputation on East-Asians. The goal is to provide a collaborative imputation platform for researchers in the public domain towards rapidly and efficiently conducting accurate genotype imputation. RESULTS: We present an online genotype imputation platform, Multi-ethnic Imputation System (MI-System) (https://misystem.cgm.ntu.edu.tw/), that offers users 3 established pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1 for conducting imputation analyses. In addition to 1000 Genomes and Hapmap3, a new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. MI-System further offers functions to create customized reference panels to be used for imputation, conduct quality control, split whole genome data into chromosomes, and convert genome builds. CONCLUSION: Users can upload their genotype data and perform imputation with minimum effort and resources. The utility functions further can be utilized to preprocess user uploaded data with easy clicks. MI-System potentially contributes to Asian-population genetics research, while eliminating the requirement for high performing computational resources and bioinformatics expertise. It will enable an increased pace of research and provide a knowledge-base for genetic carriers of complex diseases, therefore greatly enhancing patient-driven research. STATEMENT OF SIGNIFICANCE: Multi-ethnic Imputation System (MI-System), primarily facilitates, but is not limited to, imputation on East-Asians, through 3 established prephasing-imputation pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1, where users can upload their genotype data and perform imputation and other utility functions with minimum effort and resources. A new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. Utility functions include (a) create customized reference panels, (b) conduct quality control, (c) split whole genome data into chromosomes, and (d) convert genome builds. Users can also combine 2 reference panels using the system and use combined panels as reference to conduct imputation using MI-System.

The association of dry eye syndrome and psychiatric disorders: a nationwide population-based cohort study.

BACKGROUND: Several previous studies reported a greater prevalence of dry eye syndrome (DES) among patients with psychiatric diseases. The aim of this study is to investigate the prevalence and risk factors of DES in patients with psychiatric disorders (PD) using nationwide population-based data in Taiwan. METHODS: This population-based cohort study retrospectively identified patients with PD from 1997 to 2011. Patients with both PD and DES served as the DES cohort, and PD patients without DES comprised the non-DES cohort. PD was defined as a diagnosis of PD (ICD-9-CM 290-319) made by psychiatrists only, with at least three consecutive outpatient visits or at least one inpatient visit. DES was defined as a diagnosis of DES (ICD-9-CM 375.15) and a prescription for an eye lubricant (anatomical therapeutic chemical code, ATC code: S01XA). The main outcome measures were the prevalence of DES in these patients and associated risk factors. RESULTS: A total of 75,650 patients with PD (3665 in the DES cohort and 71,985 in the non-DES cohort) were included in the final analysis. The majority of patients in the DES group were women (72.6%), compared the non-DES group (57.8%). The mean age of patients in the DES cohort was 62.2 ± 14.9, which was significantly older than those in the non-DES group (50.9 ± 17.5). The patients with DES had a significantly greater likelihood of having dementia, bipolar disorder, depression, and neurotic disorders. Conditional regression analyses revealed that patients with dry eye disease were more likely to have schizophrenia (OR = 1.34), bipolar disorder (OR = 1.9), depression (OR = 1.54), and neurotic disorders (OR = 1.62). In addition, patients with DES were more likely to use 1st generation anti-psychotics (OR = 1.28) and had a lower risk of using 2nd generation anti-psychotics (OR = 0.64). CONCLUSION: The study demonstrated that among PD patients, DES is highly prevalence in certain subtypes of PD, such as depression, bipolar disorder, and neurotic disorders, after adjusting for the comorbidities.

The association between glaucoma and risk of depression: a nationwide population-based cohort study.

BACKGROUND: Previous cross-sectional studies revealed a higher prevalence of depression among glaucoma patients. However, cohort studies were in lack to build the risk of incident depression after the diagnosis of glaucoma. The aim of our study was to investigate the association between glaucoma and the subsequent risk of developing depression and to assess risk factors associated with depression in glaucoma patients. METHODS: A population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from January 1, 2001 through December 31, 2011. Glaucoma patients (n = 8777) and age- and gender-matched control subjects without glaucoma (n = 35,108) were enrolled in the study. Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent depression between the glaucoma and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the glaucoma patients. RESULTS: Glaucoma patients had a significantly higher cumulative hazard of depression compared to the control group (p-value < 0.0001). The Cox regression model indicated that the glaucoma group had a significantly higher risk of depression (adjusted HR = 1.71). Within the glaucoma group, significant risk factors for depression included age, female, low income, substance abuse, and living alone. However, the use of ß-blocker eye drops and the number of glaucoma medications were not significant risk factors for depression. CONCLUSION: Patients with glaucoma are at significantly greater risk of developing depression. Among glaucoma patients, age, female, low income, substance abuse, and living alone were significant risk factors for depression.

Analysis of the Interleukin-6 (-174) Locus Polymorphism and Serum IL-6 Levels with the Severity of Normal Tension Glaucoma.

PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. Recent studies of glaucoma or retinal ganglion cells (RGCs) reveal that the cytokine interleukin-6 (IL-6) is linked to the pathogenesis of glaucoma and may regulate RGC survival or death. The IL-6 (-174) G allele has also been shown to increase the IL-6 protein. We hypothesized that the IL-6 (-174) polymorphism may be a predisposing genetic factor affecting the severity of glaucoma. The aim of the present study was to evaluate the IL-6 polymorphism and serum IL-6 levels as a potential risk factor related to the severity of NTG. METHODS: A total of 256 subjects with NTG in the Chinese population were enrolled. The patients were genotyped for the IL-6 (-174) C/G polymorphism. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Serum IL-6 levels were measured by ELISA. Patient age at diagnosis, cup/disc (C/D) ratio, rim area (RA), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) were analyzed. The associations between genotypes of IL-6 (-174) C/G and the clinical parameters were calculated using a logistic regression. RESULTS: The IL-6 (-174) GC genotype in NTG patients was significantly associated with a smaller C/D ratio (p = 0.04), larger RA (p = 0.04), and thicker RNFL (p = 0.05) compared with IL-6 (-174) GG patients. The allele frequency of IL-6 (-174) C was significantly higher in the NTG patients at an early-moderate stage than at an advanced stage according to the C/D ratio (OR 0.55; 95% CI 0.31-0.99). Pattern standard deviation of VF was borderline lower in IL-6 (-174) GC patients (p = 0.06), and serum IL-6 levels were borderline higher in advanced stages than in early-moderate stages (7.66 ± 3.22 vs. 4.46 ± 3.83 pg/mL; p = 0.06). CONCLUSION: The IL-6 (-174) GC genotype is associated with a smaller C/D ratio, larger RA, and thicker RNFL compared with IL-6 (-174) GG in NTG patients. We found that the IL-6 (-174) G/C polymorphism and serum IL-6 levels may be associated with the severity of NTG.

Pharmacokinetics and safety of intravitreal caspofungin.

Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 µg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 µg/ml, 50 µg/ml, 100 µg/ml, and 200 µg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 µg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 µg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

Polymorphism in the TNF-α(-863) locus associated with reduced risk of primary open angle glaucoma.

PURPOSE: Tumor necrosis factor-α (TNF-α), an important proinflammatory cytokine, exerts a variety of physiologic and pathogenic effects that lead to tissue destruction. Recent laboratory evidence indicates that TNF-α have either protective or adverse effects on primary open angle glaucoma (POAG). Inheritance of the TNF-α (-863) C allele has been associated with an elevated risk of Alzheimer disease. The neuronal injuries associated with Alzheimer disease have several similarities with the optic nerve changes often seen with POAG. In this study we investigated the possible association between the TNF-α (-863) polymorphism and the development of POAG. METHODS: A total of 234 patients with POAG were recruited and compared with 230 healthy controls in a Chinese population. Sequence-specific primers with 3' end mismatches were used to identify the presence of specific allelic variants by polymerase chain reaction (PCR) amplification. Patients and controls were genotyped for the A/C polymorphism at position -863 of the TNF-α gene promoter region. RESULTS: The frequency of the TNF-α (-863)A allele (22% versus 30%, respectively; p=0.007) and the carriers of the TNF-α (-863)A allele (37% versus 48%; p=0.017, OR 0.63, 95% CI 0.44-0.92) were lower in POAG patients compared with those in controls. There is a reduced risk of POAG associated with homozygosity for the TNF-α (-863)A allele (AA genotype) compared with that in the control population (AA genotype; 7% versus 11%, respectively, p=0.037; OR 0.5, 95% CI 0.26-0.98). CONCLUSIONS: The TNF-α (-863)A allele polymorphism may be a protective factor in the development of POAG.

Epiretinal Membrane Detection at the Ophthalmologist Level using Deep Learning of Optical Coherence Tomography.

PURPOSE: Previous deep learning studies on optical coherence tomography (OCT) mainly focused on diabetic retinopathy and age-related macular degeneration. We proposed a deep learning model that can identify epiretinal membrane (ERM) in OCT with ophthalmologist-level performance. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 3,618 central fovea cross section OCT images from 1,475 eyes of 964 patients. METHODS: We retrospectively collected 7,652 OCT images from 1,197 patients. From these images, 2,171 were normal and 1,447 were ERM OCT. A total of 3,141 OCT images was used as training dataset and 477 images as testing dataset. DL algorithm was used to train the interpretation model. Diagnostic results by four board-certified non-retinal specialized ophthalmologists on the testing dataset were compared with those generated by the DL model. MAIN OUTCOME MEASURES: We calculated for the derived DL model the following characteristics: sensitivity, specificity, F1 score and area under curve (AUC) of the receiver operating characteristic (ROC) curve. These were calculated according to the gold standard results which were parallel diagnoses of the retinal specialist. Performance of the DL model was finally compared with that of non-retinal specialized ophthalmologists. RESULTS: Regarding the diagnosis of ERM in OCT images, the trained DL model had the following characteristics in performance: sensitivity: 98.7%, specificity: 98.0%, and F1 score: 0.945. The accuracy on the training dataset was 99.7% (95% CI: 99.4 - 99.9%), and for the testing dataset, diagnostic accuracy was 98.1% (95% CI: 96.5 - 99.1%). AUC of the ROC curve was 0.999. The DL model slightly outperformed the average non-retinal specialized ophthalmologists. CONCLUSIONS: An ophthalmologist-level DL model was built here to accurately identify ERM in OCT images. The performance of the model was slightly better than the average non-retinal specialized ophthalmologists. The derived model may play a role to assist clinicians to promote the efficiency and safety of healthcare in the future.

Pharmacokinetics of intracameral voriconazole injection.

Elimination of voriconazole after intracameral injection exhibited an exponential decay with a half-life of 22 min. Voriconazole levels in the vitreous humor were below the detectable limit. The aqueous concentrations achieved with a 25-microg dose during the first 2 h were greater than the previously reported MICs of organisms most involved in fungal endophthalmitis. A rapid decline in intracameral concentration suggests that frequent supplementation of intracameral voriconazole may be required in clinical settings.

Clinical Characteristics, Intraoperative Findings, and Surgical Outcomes of Canalicular Laceration Repair with Monocanalicular Stent in Asia.

PURPOSE: To report the epidemiological and clinical data as well as surgical outcomes of canalicular lacerations with Mini-Monoka insertion at a tertiary center in Taiwan and to discuss differences in traumatic pattern, pathogenesis, and surgical outcomes between Taiwan and other countries. METHODS: From 2009 to 2018, all 48 patients who underwent canalicular laceration repair with Mini-Monoka stent at a tertiary center in Taiwan were retrospectively analyzed. Demographic and clinical data and surgical outcomes were recorded. RESULTS: The mean age of the 48 patients was 38 years. Single lower canaliculus was involved in 37 (77.1%) patients, upper canaliculus in 10 (20.8%) patients, and both in 1 (2.1%) patient. The most common etiology was motorcycle accident (41.7%), and all traffic accident injuries accounted for 68.75% of cases. Subgroup classification revealed 64.6% of patients (n=31) were categorized in the deep laceration group, and lower anatomical and functional outcomes were noted in deep laceration. The mean follow-up time was 14.5 months. Overall, the anatomical success rate was 87.5%, and the functional success rate was 91.7% after stent removal. CONCLUSION: Canalicular laceration caused by traffic accidents occurred with a relatively high frequency in Taiwan. Affected patients tended to be middle-aged, and deep laceration accounted for 64.6% of patients. These were contributed by the avulsive eyelid injury mechanism caused by traffic accidents. Furthermore, the deeper lacerated site was located, and the lower anatomical and functional success rates were observed. Early repair after trauma with Mini-Monoka stents achieved good eyelid position (100%) as well as good anatomical (87.5%) and functional (91.7%) success without serious complication.

Association between Metformin and a Lower Risk of Age-Related Macular Degeneration in Patients with Type 2 Diabetes.

PURPOSE: This population-based, retrospective cohort study was to investigate whether metformin is associated with a lower risk of subsequent age-related macular degeneration (AMD) in patients with type 2 diabetes. METHODS: Using the Taiwan National Health Insurance Research Database from 2001 to 2013, 68205 subjects with type 2 diabetes were enrolled in the study cohort. Among them, 45524 were metformin users and 22681 were nonusers. The metformin and nonmetformin groups were followed until the end of 2013. Cox regression analyses were used to estimate hazard ratios (HRs) for AMD development associated with metformin use. Confounders included for adjustment were age, sex, and comorbidities (hypertension, hyperlipidemia, coronary artery disease, obesity, diabetic retinopathy, chronic kidney disease, and insulin treatment). Furthermore, propensity score (PS) matching method was used to choose the matched sample, and PS-adjusted Cox regression was performed. Finally, how HRs changed according to metformin treatment duration and dose was also evaluated in the metformin group. RESULTS: After adjusting for confounders, the metformin group had a significantly lower risk of AMD (adjusted HR = 0.54; 95% confidence interval [CI], 0.50-0.58). In the PS-matched sample, the significance remained (adjusted HR = 0.57; 95% CI, 0.52-0.63). In the metformin group, the adjusted HRs for the second (1.5-4 years) and third (≥4 years) tertiles of metformin treatment duration were 0.52 and 0.14, respectively, compared with the first tertile (<1.5 years). We also found significant trends of lower HRs (all p-value for trend <0.05) with increasing total and average doses. CONCLUSIONS: Among patients with type 2 diabetes, those who use metformin are at a significantly lower risk of developing AMD relative to individuals who do not use metformin. Also, the trend of a significantly lower AMD risk was found with a higher dose of metformin.

Association between normal tension glaucoma and the risk of Alzheimer's disease: a nationwide population-based cohort study in Taiwan.

OBJECTIVES: To investigate a possible association between normal tension glaucoma (NTG) and an increased risk of developing Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: NTG group and the comparison group were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013. PARTICIPANTS: A total of 15 317 subjects with NTG were enrolled in the NTG group, and 61 268 age-matched and gender-matched subjects without glaucoma were enrolled in the comparison group. PRIMARY AND SECONDARY OUTCOME MEASURES: Kaplan-Meier curves were generated to compare the cumulative hazard of AD between the two groups. A multivariable Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AD, adjusted for diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke. Furthermore, risk factors for developing AD among the NTG group were investigated. RESULTS: The mean age of the cohort was 62.1±12.5 years. Patients with NTG had significantly higher proportions of diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke than the comparisons. Patients with NTG had a significantly higher cumulative hazard for AD than the comparisons (p<0.0001). In the multivariable Cox regression after adjustment for confounders, the NTG group had a significantly higher risk of AD (adjusted HR 1.52; 95% CI 1.41 to 1.63). Moreover, in the NTG group, when we compared the effects of different types of glaucoma eye drops, none of the eye drops used were significant risk factors or protective factors for AD. CONCLUSIONS: People with NTG are at a significantly greater risk of developing AD compared with individuals without glaucoma. Among patients with NTG, none of the glaucoma eye drops used significantly changed the risk of subsequent AD.

Risk of Ischemic Stroke, Hemorrhagic Stroke, and All-Cause Mortality in Retinal Vein Occlusion: A Nationwide Population-Based Cohort Study.

PURPOSE: To investigate whether the risk of subsequent stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality is increased among retinal vein occlusion (RVO) patients compared to non-RVO patients. METHODS: From the entire population of the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2013, a total of 22919 subjects with RVO were enrolled in the RVO group, and 114595 propensity score (PS)-matched non-RVOs were enrolled in the comparison group. PS matching was based on age, gender, obesity, diabetes, hypertension, hyperlipidemia, coronary artery disease, atrial fibrillation, hyperviscosity syndrome, Charlson comorbidity index, glaucoma, and the use of antithrombotic drugs. A multivariate Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) with a 95% confidence interval (CI) for each of the clinical outcomes, including stroke, ischemic stroke, hemorrhagic stroke, and all-cause mortality. Furthermore, we divided the RVO group into the branch retinal vein occlusion (BRVO) group and the central retinal vein occlusion (CRVO) group and separately compared their subsequent risks of the clinical outcomes with those of the comparison group. RESULTS: After adjusting for PS, the RVO group had a significantly higher risk of stroke (adjusted HR = 1.36; 95% CI: 1.32-1.40), ischemic stroke (adjusted HR = 1.36; 95% CI: 1.32-1.40), and hemorrhagic stroke (adjusted HR = 1.34; 95% CI: 1.24-1.44). However, the all-cause mortality did not exhibit significant differences. Furthermore, both the BRVOs and CRVOs had a significantly higher risk of subsequent stroke, ischemic stroke, and hemorrhagic stroke than did the comparisons, whereas all-cause mortality was similar among the groups. CONCLUSIONS: People with RVO are at a significantly greater risk of developing stroke, ischemic stroke, and hemorrhagic stroke. However, RVO does not significantly increase the risk of all-cause mortality.

Risk of developing open-angle glaucoma in patients with carotid artery stenosis: A nationwide cohort study.

Whether carotid artery stenosis (CAS) is an independent risk factor for open-angle glaucoma remains unclear. In this study, we investigated the association between CAS and the development of open-angle glaucoma in the Taiwanese population-based cohort derived from a longitudinal database containing claims data from the Taiwan National Health Insurance (NHI) program; this study enrolled 2093 patients with CAS and 8372 patients without CAS matched by age and sex from 1999 to 2010. Diagnoses of open-angle glaucoma (OAG) were identified during a follow-up period lasting through December 31, 2013. A Cox proportional hazards model was applied to evaluate the hazard ratio (HR) for OAG in the CAS cohort compared with the matched cohort. We found that the HR for open-angle glaucoma in the CAS cohort compared with the matched cohort. The adjusted HR for OAG in the CAS cohort was 1.50 (95% confidence interval, 1.11-2.02, P = .008). The Kaplan-Meier analysis revealed that the CAS cohort had a higher cumulative incidence of OAG than did the matched cohort during the follow-up period (log-rank test, P < .001). We concluded that CAS is a significantly independent risk factor for the development of OAG. Our finding is clinically important for the aging population, which has an increasing prevalence of CAS.

Clearance of intravitreal voriconazole.

UNLABELLED: Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits. METHODS: Intravitreal injections of 35 microg/0.1 mL voriconazole were administered to rabbits. Vitreous and aqueous humor levels of voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and 48 hours), and the in vitreous half-life was calculated. Four to six eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals. Voriconazole concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography (HPLC). RESULTS: The concentration of intravitreal voriconazole at various time points exhibited exponential decay with a half-life of 2.5 hours. The mean vitreous concentration was 18.912 +/- 2.058 microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090 microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 +/- 0.051 microg/mL at 1 hour to undetectable levels 8 hours after injection. CONCLUSIONS: Vitreous concentrations achieved during the first 8 hours were greater than the previously reported minimum inhibitory concentrations (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of intravitreal concentration suggests that supplementation of intraocular voriconazole to maintain therapeutic levels may therefore be required in clinical settings. Further studies are needed to determine the elimination rate of voriconazole after intravitreal injection in humans.

Investigation of the association between interleukin-1beta polymorphism and normal tension glaucoma.

PURPOSE: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure are likely to have a role in the pathogenesis of optic neuropathy. The potential similarities in cellular apoptosis leading to neurodegeneration between Alzheimer's disease and NTG were shown in recent studies. The interleukin-1beta (IL-1beta; -511) and IL-1beta (+3953) polymorphisms were found to increase risk with Alzheimer's disease. The purpose of this study was to test the hypothesis that the IL-1beta polymorphism is associated with NTG in the Chinese population. METHODS: This is a cohort study in a Chinese population that involved 231 people with NTG and 245 healthy controls. Genomic DNA was amplified by a polymerase chain reaction, followed by the enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position -511 and +3953 of the IL-1beta gene. Genotypes for NTG and control groups were compared for statistically significant differences. RESULTS: There was no significant difference in genotype frequency or allele frequency distribution of the IL-1beta gene polymorphisms (position -511 and +3953) between NTG patients and the control group (p >0.3). CONCLUSIONS: Our study showed no evidence for an association between the IL-1beta (-511) and IL-1beta (+3953) polymorphisms and NTG. The IL-1beta gene polymorphisms (position -511 and +3953) may not play a key role in NTG pathogenesis in Chinese population.

Spontaneous resolution of partial donor disk dislocation after deep lamellar endothelial keratoplasty.

PURPOSE: We report a case of spontaneous resolution of donor disk partial dislocation after deep lamellar endothelial keratoplasty (DLEK). DESIGN: Case report. METHODS: A 70-year-old male with right pseudophakia bullous keratopathy underwent DLEK. Postoperatively, a partial dislocation of inferior donor disk was noted. Repositioning surgery with gas tamponade was performed. RESULTS: The interfacial separation remained after gas tamponade. Two weeks later, corneal edema subsided, and there was a reduction in interfacial separation. One month after DLEK, donor disk spontaneously attached to recipient corneal bed. At the six-month follow-up, astigmatism was 1.75 diopters. Specular microscopy showed endothelial counts of 1520 cells/mm(2). Spectacle-corrected visual acuity improved to 6/15. CONCLUSIONS: Partial dislocation of donor disk after DLEK has a possibility of spontaneous resolution, even after a failed attempt at gas tamponade.

Progressive herpetic linear endotheliitis.

PURPOSE: To report the clinical course of a rare case of bilateral herpetic linear endotheliitis. METHODS: A 70-year-old man presented with bilateral circumferential bullous edema with stromal edema progressing centrally in the left cornea and bilateral sensorineural hearing impairment simultaneously. Serum immunoglobulin G (IgG) and IgM antibodies against herpes simplex virus type 1 (HSV1) were tested for, and aqueous humor from both eyes was examined separately using polymerase chain reaction for the presence of HSV1 DNA. RESULTS: Serum antibody titers against HSV1 were positive. In the polymerase chain reaction, the aqueous humor showed HSV1 DNA in both eyes. Forty milligrams of prednisolone was given per day and 200 mg of oral acyclovir was given 4 times daily, but corneal edema progressed. After penetrating keratoplasty surgery in the left eye, recurrent herpetic endotheliitis also seemed to occur. CONCLUSIONS: HSV-1 may cause bilateral corneal linear endotheliitis and hearing impairment simultaneously. Linear endotheliitis should be regarded as a manifestation of HSV1 corneal infection. There is a poor prognosis, and severe corneal edema can result if aggressive treatment is not used.

Supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis.

PURPOSE: To evaluate the efficacy of supratarsal triamcinolone injection in the treatment of superior limbic keratoconjunctivitis (SLK). METHODS: Forty eyes of 20 patients were diagnosed with SLK. All eyes with long-standing severe ocular irritation unresponsive to topical steroid and artificial tears were treated with supratarsal triamcinolone injection in addition to ongoing treatment of dry eye. Objective tarsal conjunctiva inflammation, bulbar conjunctiva, cornea staining, and subjective symptom gradings were performed before and after 2 weeks of therapy. All patients underwent laboratory evaluations of underlying systemic abnormalities. RESULTS: All 40 eyes responded well to treatment and had long-term (average, 7.8 months) improvement of irritation and dry sensation and improvement of inflammation and staining of conjunctiva and cornea. Fourteen patients (70%) had associated autoimmune diseases. There were no irreversible complications related to this therapy. CONCLUSIONS: Supratarsal triamcinolone injection effectively and rapidly resolved symptoms and signs associated with SLK. It is helpful as primary or adjunctive therapy for SLK.

Normal tension glaucoma is not associated with the interleukin -1alpha (-889) genetic polymorphism.

BACKGROUND: Factors other than intraocular pressure are likely to play a role in the pathogenesis of glaucomatous optic neuropathy, particularly in individuals with normal tension glaucoma (NTG). Recent laboratory evidence has shown that there are potential similarities between Alzheimer disease and NTG in cellular apoptosis leading to neurodegeneration. IL-1alpha (-889) T allele polymorphism has been found to increase the risk of developing Alzheimer disease. The aim of this study was to test in a Chinese cohort the hypothesis that IL-1alpha (-889) polymorphism is associated with NTG. METHODS: One hundred sixty-two unrelated patients with NTG were recruited and compared with 167 controls in a Chinese population. Genomic DNA was amplified by polymerase chain reaction, followed by enzymatic restriction fragment length polymorphism technique. Patients and controls were genotyped for the C/T polymorphism at position -889 of the IL-1alpha gene promoter region. RESULTS: There was no significant difference in the frequency of IL-1alpha (-889) alleles or genotypes in the NTG population compared with that in the control group. CONCLUSIONS: We conclude that C/T polymorphism at position -889 of the IL-1alpha gene promoter region does not increase the risk of developing NTG. However, further studies on NTG are necessary to investigate the genetic basis and factors involved in the development of the neurodegenerative process.

Pax6 overexpression suppresses cell proliferation and retards the cell cycle in corneal epithelial cells.

PURPOSE: The gene encoding transcription factor Pax6 resides at the top of a genetic hierarchy controlling development and morphogenesis of the eye. Pax6 continues to be expressed in the ocular surface epithelia of the postnatal eye. The goal of this study was to investigate a possible role for Pax6 in controlling dynamics of the ocular surface epithelia. METHODS: Full-length mouse Pax6 (mPax) cDNA, or truncated mPax6Delta286 lacking the transcriptional activation domain was inserted into a tetracycline-inducible vector (Tet-on). A rabbit corneal epithelial cell line SIRC was used to establish stable transformants. Induction of Pax6 or truncated Pax6Delta286 proteins by doxycycline (DOX) was examined by Western blot and immunohistochemistry. The effects of Pax6 overexpression on cell cycle progression were assessed by the cell proliferation index, cell growth curve, and cell cycle assay. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) assay was performed to detect apoptotic cells. Recombinant adenovirus-carrying mPax6 or mPax6Delta286 transgenes were used for transient transduction of primary rabbit corneal epithelial cells, and the effect on cell cycle progression was assayed. RESULTS: The level of Pax6 or truncated Pax6 was tightly regulated by DOX. Overexpression of full-length Pax6 retarded the rate of cell proliferation, whereas the truncated form had no effect. Full-length Pax6 affected the rate at which individual cells traversed the cell cycle and induced caspase-3-independent apoptosis in a small percentage of cells. Transient transduction of cells with recombinant mPax6 adenovirus also inhibited cell proliferation. CONCLUSIONS: Inhibition of cell proliferation in Pax6-overexpressing corneal epithelial cell lines and primary cell culture is consistent with the notion that Pax6 plays a role in controlling corneal epithelial cell dynamics in vivo.