Automated Classification of Inherited Retinal Diseases in Optical Coherence Tomography Images Using Few-shot Learning / 生物医学与环境科学（英文）

OBJECTIVE@#To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs).@*METHODS@#In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples.@*RESULTS@#The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications.@*CONCLUSION@#This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.

Analysis of Radial Peripapillary Capillary Density in Patients with Bietti Crystalline Dystrophy by Optical Coherence Tomography Angiography / 生物医学与环境科学（英文）

OBJECTIVE@#We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD).@*METHODS@#We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two.@*RESULTS@#The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD.@*CONCLUSION@#The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.

Optical Coherence Tomography Features of Tuberculous Serpiginous-like Choroiditis and Serpiginous Choroiditis / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate optical coherence tomography (OCT) characteristics of tuberculous serpiginous-like choroiditis (Tb-SLC) and serpiginous choroiditis (SC) and to perform OCT to differentiate between these conditions.</p><p><b>METHODS</b>This retrospective, case-control study examined consecutively enrolled patients with active Tb-SLC or SC. Patients underwent comprehensive ocular examinations and imaging (OCT, color fundus photography, autofluorescence imaging, fluorescein angiography, and indocyanine green angiography). Findings were examined and compared between eyes with SC and Tb-SLC.</p><p><b>RESULTS</b>Nine patients with active Tb-SLC (14 eyes) and 8 with active SC (12 eyes) were included. The following OCT findings were observed significantly more often in the Tb-SLC group than in the SC group: vitreal hyper-reflective spots [5 Tb-SLC eyes (36%), no SC eyes; P = 0.02], intraretinal edema [11 Tb-SLC eyes (79%), 3 SC eyes (25%); P = 0.01], sub-retinal pigment epithelium (RPE) drusenoid deposits [11 Tb-SLC eyes (79%), 2 SC eyes (17%); P < 0.01], and choroidal granulomas [8 Tb-SLC eyes (57%), 2 SC eyes (17%); P = 0.03]. A hyporeflective, wedge-shaped band was observed more often in the SC group [5 Tb-SLC eyes (36%), 9 SC eyes (75%); P = 0.045] than in the Tb-SLC group. The incidence of other OCT signs did not differ between the groups and included outer nuclear layer hyper-reflection, outer retinal tabulation, and choriocapillaris point-like hyper-reflection.</p><p><b>CONCLUSION</b>Vitreal hyper-reflective spots, intraretinal fluid, sub-RPE drusenoid deposits, and choroidal granulomas on OCT images may indicate Tb-SLC. Additionally, a hyporeflective, wedge-shaped band may indicate SC. Therefore, OCT is likely helpful in differentiating between Tb-SLC and SC.</p>

Gitelman syndrome: From pathophysiology to clinical practice / 国际药学研究杂志

Normal tubular transport function is important for maintaining the volume of fluid and electrolyte in the body. Advances in molecular biology have revealed the genetic regulation and pathophysiological mechanisms of inherited tubular disorders. This progress not only sheds some light on the clinical practice, but also leads to better understanding of the normal tubular structures and function. As the most common inherited tubular disorders, Gitelman syndrome (GS) is an autosomal recessive inherited disease, mainly caused by loss-of-function mutations in the SLC12A3 gene encoding the sodium-chloride co-transporter (NCC) in the distal convoluted tubule. This review summarizes some of the recent progress in genetic diagnosis, in vivo and in vitro functional studies and management of GS.

Reduction on OFF-responses of Electroretinogram in Monkeys with Long-term High Intraocular Pressure / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There are ON- and OFF-pathways in the normal vertebrate retina. Short- and long-flash electroretinogram (ERG) are suitable methods to observe the function of ON- and OFF-pathways in vivo, respectively. It is clear that high intraocular pressure (IOP) might cause dysfunction of cone-dominated photopic negative response (PhNR) in monkeys with high IOP in ON-pathway. However, whether cone-dominated OFF-responses are also affected is less known. The aim of this study was to observe photopic OFF-responses of ERG in monkeys with high IOP.</p><p><b>METHODS</b>Nine monkeys were involved in the experiment from January 2006 to December 2016. High IOP was induced in the right eye by laser coagulation of the mid-trabecular meshwork in five monkeys. Six years after the laser coagulation, both short- and long-flash of the photopic ERG were recorded. Stimulus light was red flashes superimposed on a blue background. Four normal monkeys were examined under the same ERG protocols as controls. Paired t- test was used to compare the difference of each ERG parameter between the lasered eye and the fellow eye. Analysis of variance (ANOVA) with Tukey adjustment was adopted to calculate the differences among the lasered eye, the fellow eye, and the eyes of normal monkeys.</p><p><b>RESULTS</b>The mean amplitude of a-wave (11.73 ± 2.05) and PhNR (8.67 ± 2.44) in lasered eyes was significantly lower than that of a-wave (21.47 ± 3.15) and PhNR (22.05 ± 3.42) in fellow eyes (P = 0.03 and P = 0.01, respectively) in response to short flash. The mean amplitude of d-wave (1.60 ± 0.59) and i-wave (3.13 ± 0.64) was significantly reduced in the lasered eyes than that of d-wave (4.01 ± 0.56) and i-wave (8.79 ± 1.75) in the fellow eyes (P = 0.02 and P = 0.02, respectively) in response to long flash.</p><p><b>CONCLUSIONS</b>Reduced OFF-responses are recorded in monkeys with high IOP when dysfunction of photoreceptor is involved. The reduced OFF-responses to long-flash stimulus show evidence of anomalous retinal circuitry in glaucomatous retinopathy.</p>

Value of Chloride Clearance Test in Differential Diagnosis of Gitelman Syndrome / 中国医学科学院学报

Objective To investigate the value of chloride clearance test in differential diagnosis of Gitelman syndrome (GS). Methods For patients with hypokalemic metabolic alkalosis and highly suspected GS,clinical data were documented and SLC12A3 gene screening was performed as gold standard to diagnose GS. Hydrochlorothiazide (HCT) test and furosemide (FUR) test were performed according to the standard process. Baseline and maximal increasement of chloride excretion fraction (FECl,the net and relative increase measured as εFECl) were compared between patients and controls to evaluated the reaction to the corresponding diuretics. Receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of HCT test in GS diagnosis. Results Totally 27 patients and 20 health controls received HCT test. Among those patients,23 were diagnosed with GS genetically. When using the net and relative εFECl to diagnose GS,the areas under the ROC curve were 0.987 (95% CI:0.963～1.000,P<0.001) and 0.984 (95%CI:0.950～1.000,P<0.001),respectively. When a reasonable cutoff value for εFECl was selected,the sensitivity and specificity were both higher than 95%. Eight patients received both HCT test and FUR test. Five of them showed decreased reaction to HCT(net εFECl≤2.86% or relative εFECl≤223%),while normal reaction to FUR.SLC12A3 mutations confirmed their GS. Three patients with blunt reaction to FUR showed normal reaction to HCT,finally they were diagnosed as BS clinically because no SLC12A3 gene mutation was detected. Conclusion Comprehensive application of HCT test and FUR test to evaluate the diuretic reaction can effectively differentiate GS and BS.

Effect of orexin-A and orexin-1 receptor antagonist injected into the fourth ventricle of rats on food-intake and spontaneous physical activity / 生理学报

The present study was aimed to investigate the effects of orexin-A and orexin-1 receptor (OX1R) antagonist injected into the fourth ventricle of rats on food-intake and spontaneous physical activity (SPA). Obese rat model was induced by high fat diet. Different doses of orexin-A or SB334867, an OX1R antagonist, were injected into the fourth ventricle of obese and normal rats respectively. SPA and food intake were monitored for 4 h after injection in both light and dark environment. In the light measurement cycle, different doses of orexin-A significantly stimulated feeding and SPA in all injected rats, and the animals' responses showed a dose-dependent manner (P < 0.05-0.01), and compared with those of normal rats, the orexin-A induced food intake and SPA were more pronounced in obese rats. In the dark measurement cycle, different doses of orexin-A had no obvious effect on food intake and SPA in both normal and obese rats (P > 0.05). In the light cycle, different doses of SB334867 significantly decreased food intake and SPA in all rats during 0-2 h and 2-4 h after injection (P < 0.05), but the food intake and SPA in obese rats were significantly greater than those of normal rats. In the dark cycle, different doses of SB334867 showed no obvious effect on food intake and SPA of normal and obese rats (P > 0.05). These results suggest that fourth cerebral ventricle nuclei may be one target for orexin-A and light condition may play an important role in orexin-A and OX1R physiological functional processes.

Hyperglycemic effects of a periocular dexamethasone injection in diabetic patients after vitreoretinal surgery / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To examine the hyperglycemic effects of periocular dexamethasone injection in type 2 diabetic patients after vitreoretinal surgery (VRS).</p><p><b>METHODS</b>This was a retrospective non-randomized controlled trial. Twenty consecutive hospitalized patients with type 2 diabetes and ocular inflammatory reaction after VRS were enrolled in this study. Ten patients received 2.5 mg dexamethasone and 10 patients received 5 mg dexamethasone. Fourteen consecutive type 2 diabetic patients without ocular inflammatory reaction after VRS were used as control group. We measured fasting blood glucose (FBG) and at 2 h after each meal (post prandial glucose, PBG; 09:00, 13:00, and 19:00 h) after periocular dexamethasone injection. Differences among three groups were determined by q tests.</p><p><b>RESULTS</b>The PBG levels in both dexamethasone-treated groups started to increase within 5 h after injection (i.e., PBG at 13:00 h), and were significantly increased at 19:00 h after injection (P<0.05). BG levels were almost 2-fold higher than at baseline and compared with the control group. The BG values declined gradually by 24 h to 48 h after injection. There were no differences in BG levels between the two dexamethasone-treated groups (P>0.05), except for PBG at 19:00 h on day 2 after injection (P<0.05).</p><p><b>CONCLUSION</b>Periocular dexamethasone injection can cause transient hyperglycemia in diabetic patients after VRS. BG monitoring should be performed following such injection.</p>

The clinical characters of tear film instability in diabetes patients / 中华实验眼科杂志

Background The current epidemiology study had shown the prevalence of age and sex adjusted dry eye was higher in patients with diabetes than population without diabetes.Further researches demonstrated that the tear film disturbance is common after the phacoemulsification or photocoagulation in the eyes of diabetic patients.Objective The aim of this study was to characterize the clinical features of tear film instability in diabetes patients.Methods One hundred and sixty-two patients with tear-film abnormality referred to Tongren Eye Center from January 1,2010 to September 1,2010 underwent questionnaire about diabetes and other diseases,BUT,Schirmer test.Tear film instability was diagnosed as abnormality of either Schirmer test or BUT and showed as M ( Q25,Q75 ).The right eyes of 162 dry eye patients meeting with the including criteria were enrolled.The patients were assigned to two groups according to with ( 80 patients) or without ( 82 patients) diabetes mellitum.DEQ questionnaire were scored.The percentage of cases with meibomain gland abnormal score ＞ 1 was calculated.Mann-Whitney U analysis and Chisquare analysis were used to compare the difference between the two groups.Results The Schirmer test in diabetic group was 8 ( qualities:5,9 )mm and was longer than 6 ( qualities:5,7 ) mm in non-diabetic patients ( U =2452,P =0.00).The result of BUT test was 3 ( qualities:2,4 ) seconds in diabetic patients and was shorter than 4 (qualities:3,5) seconds in non-diabetic patients( U=2104,P＜0.01 ).The DEQ score of diabetic patients was 15 ( qualities:1 0,19,which was less than21 ( qualities:19,23.25 ) in non-diabetic patients.51.2 ％ ( 41/80 ) diabetic participants and 32.9％ (27/82) nondiabetic participants appeared meibography ( grade larger than 1 ) (x2 =16.07,P=0.00).The percentages of dry eyes were 51.2％ (41/80) and 93.9％ (77/82) respectively in diabetes and nondiabetes groups(x2 =37.24,P＜0.01 ).No significant correlation was found between the diabetes course and DEQ score or meibography( r =0.16,P =0.16 ; r =0.10,P =0.36 ).Conclusions Diabetes patients with tear film instability have longer Schirmer test results,shorter BUT,more severe meibomain glands damage and lower DEQ scores.The dry eye symptom is lack in the diabetic patients though appearing the tear film and meibomain glands damage.Therefore,more attention should be given to ocular surface health in diabetes patients.

Penetrability of interleukin-1beta and its effect on the concentration of tumor necrosis factor-alpha and interleukin-6 in the aqueous humor of rabbits treated with interleukin-1beta / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin (IL)-1beta may effectively decrease introcular pressure (IOP) when administered by subconjunctival injection in normal rabbit. However, IL-1beta is a large molecular agent and an inflammation factor. The aim of this study was to evaluate the penetrability of IL-1beta, and the concentrations of both tumor necrosis factor (TNF)-alpha and IL-6 in the aqueous humor of normal rabbits treated with IL-1beta.</p><p><b>METHODS</b>A total of 170 rabbits were used in the study and were assigned to several different treatment groups as follows: 125 of the rabbits were assigned to two groups. In one group, 33 rabbits were injected subconjunctivally with IL-1beta and 39 were injected with saline alone. In the other group, 27 rabbits were given eye drops containing IL-1beta (400 ng/ml) and 26 were given saline alone. Aqueous humor (AH) was drawn and the concentration of IL-1beta within the fluid measured. The IOP was measured in another six rabbits after administration of eye drops containing IL-1beta (400 ng/ml). A further 20 rabbits were assigned to 3 groups as follows: eight untreated normal controls; six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of TNF-alpha in the fluid was measured. Another 19 rabbits were assigned to 3 groups as follows: seven untreated normal controls; and six injected subconjunctivally with IL-1beta; and six injected subconjunctivally with saline alone. AH was drawn and the concentration of IL-6 in the fluid measured. Measurement of cytokine concentration was by radio-immunoassay in all cases.</p><p><b>RESULTS</b>The IL-1beta concentration in the AH was higher in those animals in which it had been administered subconjunctivally (P < 0.01). The IL-1beta concentration in the AH of the animals given eye drops was almost the same as that in the controls (P > 0.05). The administration of IL-1beta in the form of eye drops had little effect upon IOP reduction. Lower TNF-alpha concentrations were seen in the AH after the subconjunctival administration of IL-1beta, but the concentration of IL-6 was the same as in the normal controls.</p><p><b>CONCLUSIONS</b>IL-1beta shows good corneal penetrability after subconjunctival injection into normal rabbit eyes. The IOP reduction induced by IL-1beta is unlikely be associated with an inflammatory response.</p>

An increased expression of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease / 国际眼科杂志(Guoji Yanke Zazhi)

· AIM: To investigate the expression and the possible implication of CD40/CD40L costimulatory molecules in erythema nodosum of patients with Beh(c)et's disease.· METHODS: Sampling was done from erythema nodosum of 5 patients with Beh(c)et's disease and normal skin of 2 healthy individuals. Immunohistochemical staining was performed to examine the expression of CD4, CD8, CD19, CD68, HLA-DR,CD40 and CD40L molecules in the obtained tissues.· RESULTS: Approximately 90% of epidermic cells in erythema nodosum expressed CD40 molecule. In the dermis and subcutaneous tissue, a significantly increased number of CD4+Tcells, CD8+Tcells, CD19+cells, CD68+cells, HLA-DR+cells,CD40L+cells, and CD40+cells were observed in the erythema nodosum as compared with that in normal skin. Double staining showed that CD40L molecules were expressed on 45% of CD4+T cells. CD40 molecules were expressed on 100% CD68+ cells and 59.2% of HLA-DR+cells respectively.· CONCLUSION: A number of CD40/CD40L costimulatory molecules are upreguiated in the erythema nodosum of patients with Behcet's disease.

Comparative investigation of intravitrous levels of hepatocyte growth factor in diabetic neovascular glaucoma / 眼科

Objective To examine the concentrations of hepatocyte growth factor(HGF)and vascular endothelial growth factor (VEGF)in the patients with diabetic neovascular glaucoma(NVG),proliferative retinopathy without neovascularization of the iris(PDR) and idiopathic macular role(IMH),and to determine the relationship between HGF and VEGF.Design Prospective case series. Participants 14 patients(14 eyes)with NVG,22 patients(22 eyes)with non-NVI PDR,19 patients(19 eyes)with IMH.Methods The double-antibody sandwich enzyme-linked immunosorbent assay(ELISA)was used to measure the intravitreous level of HGF and VEGF.Main Outcome Measures The concentrations of HGF and VEGF in the same specimens.Results The concentrations of HGF (mean?SD)in vitreous of NVG group,PDR group and IMH group were(12908.42?2946.46)、(9770.86?3802.99)、(4160.54?2044.80)pg/ ml,respectively(Kruskal-Walls test,X~2=32.36,P=0.000).In addition,significant differences were observed between groups of the concentrations of HGF(P＜0.01,respectively).The intravitreous concentrations of VEGF(mean?SD)in three groups were(823.50?718.58)、(821.82?786.27)、(22.73?3.20)pg/ml(X~2=28.30,P=0.O00),respectively(Kruskal-Walls test,X~2=32.36,P=0.000).There was no significant correlation between the concentrations of HGF and those of VEGF in the same specimens from each group(P＞0.05, respectively).Conclusions The intravitreous concentrations of HGF in the patients with diabetic NVG are obviously higher than those with IMH and non-NVI PDR,suggesting that HGF appears to be associated with mediating the neovascularization of retina and iris in NVG.However,it is not found there is any relationship between the intravitreous levels of HGF and VEGF.