Tianjin Medical University Eye Hospital Research Articles

The observation of secretogranin Ⅲ in the peripheral blood and vitreous of patients with diabetic retinopathy

Objective: To study the expression levels of secretogranin Ⅲ (SCG3) in the peripheral blood and vitreous of patients with diabetic retinopathy (DR). Methods: Cross-sectional research. A total of 77 patients (41 men and 36 women, 77 eyes) received vitrectomy in Tianjin Medical University Eye Hospital from May to December 2018, with an average age of (60.75±11.34) years. According to the blood glucose level, diabetes history and fundus status, all the patients were divided into the DR group and the non-diabetic group. According to the patients' blood lipids and body mass index (BMI), patients were further divided into subgroups of high blood lipids, normal blood lipids, high BMI and normal BMI. All patients were tested with eye examinations, height and weight to calculate the BMI, and blood lipid levels in the peripheral blood. The vitreous was collected during the vitrectomy surgery, and the levels of SCG3 in the vitreous and peripheral blood were analyzed by ELISA. All the data were analyzed statistically with Wilcoxon rank sum test. Results: There were 43 patients in the DR group, among whom 25 had hyperlipidemia, 18 had normal blood lipids, 22 had a high BMI, and 21 had a normal BMI. There were 34 patients in the non-diabetic group, among whom 13 had hyperlipidemia, 21 had normal blood lipids, 17 had a high BMI, and 17 had a normal BMI. The level of SCG3 in the DR group [6.02 (4.34, 11.76) ng/ml] was higher than that in the non-diabetic group [4.30 (3.20, 10.78) ng/ml] (Z=-2.339, P =0.019). The level of SCG3 in the hyperlipidemia subgroup of the DR patients [7.94 (5.33, 13.51) ng/ml] was higher than that in the normal blood lipid subgroup of the non-diabetic patients [4.04 (3.12, 7.77) ng/ml] (Z=-3.473, P=0.001), and higher than that in the DR patients without hyperlipidemia [4.45 (3.71, 9.14) ng/ml] (Z=-2.511, P=0.012). The level of SCG3 in the DR patients with a high BMI [7.12 (4.56, 13.12) ng/ml] was higher than that in the non-diabetic patients with a normal BMI [3.53 (3.16, 4.38) ng/ml] (Z=-3.767, P =0.000). The level of SCG3 in the DR patients with a normal BMI [5.72 (4.10, 11.60) ng/ml] was higher than that in the non-diabetic patients with a normal BMI (Z=-2.862, P = 0.004). SCG3 in the plasma was rare or can not be detected. Conclusions: The concentration of SCG3 in the vitreous increase in DR patients. However, SCG3 can not be detected in the healthy vascular system. (Chin J Ophthalmol, 2020, 56: 933-937).

Clinical Analysis of Castleman's Disease of the Lacrimal Gland.

Objective To explore the clinical manifestations, imaging characteristics, and pathological characteristics of Castleman's disease of the lacrimal gland, enhance the knowledge of the disease, and improve the level of its diagnosis and treatment. Methods In the retrospective study, the data of 5 patients diagnosed with Castleman's disease of the lacrimal gland in Tianjin Medical University Eye Hospital from 2014 to 2018 were analyzed, and the relevant literature was reviewed. Results All the 5 patients were confirmed by pathological examination. Clinical manifestations were characterized by mass occupying lesions in the lacrimal gland area, without obvious pain, accompanied by eyelid swelling and ptosis, as well as space-occupying symptoms. Imaging examination showed that there was a soft tissue mass in the enlarged lacrimal gland area, and the mass was rich in blood flows while showing no obvious specificity, which could invade the surrounding muscles. All patients underwent surgical resection. Pathological results showed that 1 case was of the hyaline-vascular type, 3 cases were of the plasma cell type, and 1 case showed malignant transformation to plasma cell tumor. Conclusion Castleman's disease of the lacrimal gland is a rare orbital lymphoproliferative disease lacking specificity in clinical manifestations and imaging examination. As there are difficulties in differentiating the disease from orbital inflammatory pseudotumor and orbital lymphoma, its diagnosis still depends on pathological examination. The disease is mainly treated with surgical resection, and the pathological type is determined postoperatively.

Postoperative severe visual impairment: surgical outcome of 165 patients with orbital tumours in the muscle cone.

This study aimed to evaluate the risk factors of postoperative severe vision impairment (PSVI) for a primary orbital tumour in the muscle cone. A retrospective analysis of the patients who underwent orbitotomy for primary intraconal tumours at the Tianjin Medical University Eye Hospital from January 2010 to December 2015. A total of 165 cases of orbitotomy for primary orbital tumours in the muscle cone were included in the study. Postoperatively, 12 cases with vision acuity ≤20/400 or ≥4 rows of vision decline and without any corrected effect were analysed as PSVI, including no light perception (NLP) for 3 cases. The multivariate logistic regression indicated that the tumour in orbital apex (P = 0.048, OR = 4.912, 95% CI: 1.011-23.866), severe optic nerve displacement (P = 0.030, OR = 6.007, 95% CI: 1.184-30.473) and intraoperative tight adhesion (P = 0.003, OR = 12.031, 95% CI: 2.282-63.441) were the independent risk factors for PSVI. The incidence of PSVI for the intraconal tumour was 7.3%, and the incidence of NLP was 1.8%. The tumour in orbital apex, severe optic nerve displacement and intraoperative tight adhesion were independent risk factors for PSVI.

Cohort study of genotype and clinical phenotype in 34 families with familial exudative vitreoretinopathy

Objective To observe and analyze the genotype and clinical phenotype in 34 families of familial exudative vitreoretinopathy associated with (FEVR) gene variation. Methods Cohort study. Thirty-four FEVR families, in which the patients and both of their parents were all found to have FEVR-related gene mutations (proband 34 cases, 67 eyes; parents 68 cases, 136 eyes), were included in the study. These patients were identifIed from 722 FEVR patients through genetic screening, which diagnosed in Department of Ophtalmology of Xinhua Hospital and Tianjin Medical University Eye Hospital from January 2010 to December 2018. The probands and their parents underwent a comprehensive ophthalmological examination appropriate to their age, including BCVA, intraocular pressure, axial length, slit lamp examination, indirect ophthalmoscopy, FFA or color fundus photography or wide field color fundus photography. According to the severity of the disease, the clinical manifestations were divided into severe phenotype and mild phenotype. Thirty-four normal healthy people over 40 years old were included as the control group. The peripheral blood samples of FEVR family members and control group members were collected, and the genes known to be involved in FEVR, such as FZD4, LRP5, NDP, TSPAN12, ZNF408 and KIF11, were analyzed by next generation sequencing molecular genetics. The data were statistically analyzed by SPSS. The counting data was expressed in numbers or rates, and tested by Kruskal-Wallis test and χ2 test to find out the existence of significant difference. Results In 67 eyes of the 34 probands, 48 eyes (71.64%) were classified into severe phenotype and 19 eyes (28.36%) were mild phenotype. In 136 eyes of 68 parents of the proband patients, 76 eyes (55.88%) were normal, 60 eyes (44.12%) were classified into mild phenotype, and no severe phenotype was found. A total of 65 variants of FEVR-related genes were detected in the 34 probands, of which LRP5 mutation was the most common (64.61 %), followed by FZD4 (12.31%), NDP (10.77%), TSPAN12 (6.15%), ZNF408 (4.62%) and KIF11 (1.54%). Missense mutations were the most common variant in FEVR-related genes. However, the results of correlation analysis indicated that there was no significant correlation between the type of mutation and the severity of clinical phenotype (H=1.775, P=0.620). Among the 65 mutation types, 21 types have been previously identified and 44 were novel in this study. Thirty-nine eyes of 20 cases had only one single pathogenic mutation gene but with multiple mutation sites, 26 eyes of 13 cases carried 2 relevant pathogenic mutation genes, and 2 eyes in one case had 3 pathogenic mutation genes. The mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in probands were significantly higher than those in control group, and the difference was statistically significant. The total mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in proband group were significantly higher than those in control group (χ2=64.702, P <0.001). Conclusions In the FEVR families, the most frequent mutations were those in LRP5, followed by FZD4, NDP, TSPAN12,ZNF408 and KIF11. Missense mutation is the most common type of FEVR-related gene mutation, but there is no significant correlation between the clinical phenotype and gene variation type. Most of the probands were with severe clinical phenotype, while most of the parents with FEVR pathogenic gene mutation showed normal or mild manifestations. Key words: Retinal diseases/genetics; Genotype; Mutation; Familial exudative vitreoretinopathy

Intravitreal injection of conbercept after operation in the treatment of proliferatived diabetic retinophathy complicated with vitreous hemorrhage

Objective To observe the efficacy and safety of intravitreal injection of conbercept in the treatment of proliferatived diabetic retinophathy (PDR) complicated with vitreous hemorrhage by minimally invasive vitreoretinal surgery. Methods Prospective clinical study. A total of 50 patients with PDR complicated with vitreous hemorrhage clinically diagnosed in Tianjin Medical University Eye Hospital who needed vitrectomy were recruited in this study. According to the principle of informed consent, the patients were divided into two groups: postoperative injection group and the control group. Twenty-five eyes of 25 patients in each group were examined before operation. No significant proliferative changes in the posterior pole and traction retinal detachment were observed. There was significant difference of age between two groups (t=-24.697, P=0.030), but no significant difference of sex (χ2=0.330, P=0.564), duration of diabetes (t=-1.144, P=0.258), logMAR BCVA (t=-0.148, P=0.883), lens state (χ2=0.397, P=0.529), panretinal laser photocoagulation (χ2=1.333, P=0.248). The postoperative injection group was treated with intravitreous injection of 0.05 ml conbercept (10 mg/ml) immediately after 27G minimally invasive vitrectomy. The other treatment and follow-up were the same as those in the postoperative injection group except for conbercept injection. All patients underwent routine slit-lamp examination, indirect ophthalmoscope and B-ultrasound examination before operation. The main outcome measure included the time of operation, the incidence rate of iatrogenic retinal holes and silicone oil filling. The recurrence of vitreous hemorrhage, BCVA, intraocular pressure, central retinal thickness (CRT), postoperative complications and progression were recorded 1 week, 1 month, 3 months and 6 months after operation. Results At 1 week and 1, 3, 6 months after operation, there was significant difference of logMAR BCVA between the two groups (t=-4.980, -4.840, -4.892, -5.439; P<0.001). At 3 and 6 months after operation, the recurrence of vitreous hemorrhage in the postoperative injection group was lower than that in the control group, but there was no statistical difference between two groups (χ2=3.030, 4.153; P=0.192, 0.103). At 1 week and 1, 3, 6 months after operation, the CRT in the postoperative injection group was lower than that in the control group, the difference was significant (t=-2.622, -2.638, -3.613, -3.037; P=0.012, 0.010, 0.001, 0.004, 0.005). There was no complications such as choroid detachment, proliferative vitreoretinopathy, retinal detachment, iris redness and neovascular glaucoma in all the eyes after operation. Conclusions Intravitreal injection of conbercept in the treatment of PDR after operation is safe and effective. It can reduce the recurrence of vitreous hemorrhage after vitrectomy, improve the BCVA. Key words: Diabetic retinopathy/complications; Vitreous hemorrhage; Angiogenesis inhibitors/therapeutic use; Vitrectomy

Differential expression and bioinformation analysis of retinal proteins in mice with experimental autoimmune uveitis

Objective To observe the expression of retinal proteins in experimental autoimmune uveitis (EAU) mice and to explore the possible molecular mechanism of autoimmune uveitis. Methods Twelve female C57BL/6J mice were randomly divided into model group and normal control group, 6 mice in each group.In the model group, the EAU model was established by subcutaneous injection of human interphotoreceptor retinoid-binding protein (IRBP) 651-670.The fundal change of EAV mice was assessed by direct ophthalmoscope, OCT and histopathological staining.At 18 days after immunization, the retinas of the two groups were taken for retinal protein extraction, protein restriction enzyme digestion, mass spectrometry detection, data analysis, and bioinformatics analysis.This study was approved by the experimental animal Ethics Committee of Tianjin Medical University Eye Hospital (TJYY2018070113). The feeding and use of experimental animals follow the ARVO statement. Results The EAU mouse model was successfully established.At 10 days after immunitation, the retina of EAV mouse was damaged.At 18 days after immunization, retinal edema and infiltration of inflammatory cells into vitreous were observed.Proteomic results showed that a total of 4 458 proteins were identified in this study, of which 522 were differentially-expressed proteins (fold change>1.5, P<0.05). Among these differentially-expressed proteins, 147 proteins including Stat1 and Stat3 were up-regulated and 375 proteins including Gucy2f and Rho were down-regulated.These differentially-expressed proteins were closely related to platelet activation, integrin signaling, T cell activation, the phototransduction cascade, Toll-like receptor and so on. Conclusions EAU is related to the abnormal expression of Stat1, Stat3 and other proteins, as well as the abnormal regulation of platelet activation and integrin signal pathway. Key words: Uveitis/immunity; Retina; Autoimmune diseases; Proteomics; Mice, inbred C57BL

Regulation of human umbilical cord mesenchymal stem cells derived exosomes on peripheral blood macrophages from rabbit autoimmune dry eye

Objective To investigate the effect of human umbilical cord mesenchymal stem cells derived exosomes (hUC-MSC-exo) on the phenotype of peripheral blood macrophages from rabbit autoimmune dry eye and the expression of related cytokines. Methods The hUC-MSCs were isolated and characterized.Exosomes derived from hUC-MSCs were extracted by ultracentrifugation and observed directly using electronic microscopy.Specific markers of exosomes were analyzed by Western blot.Six rabbits were randomly divided into the normal control group and the dry eye group by using the random number table method, 3 rabbits for each group.Rabbit model of autoimmune dry eye was established in the dry eye group, and the lacrimal glands were collected for quantitative real-time PCR (qRT-PCR) at the 8th week.In vitro, activated peripheral blood mononuclear cells (PBMCs) from rabbit autoimmune dry eye model were incubated with hUC-MSC-exo or phosphate buffered saline (PBS). After 48 hours, cells from the hUC-MSC-exo group and the PBS control group were collected.The mRNA expression levels of related cytokine genes and subpopulation-related marker genes in macrophages were quantified by qRT-PCR.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.This study protocol was approved by Ethic Committee of Tianjin Medical University Eye Hospital (No.TJYY20181217001). Written informed consent was obtained from each family before obtaining umbilical cord. Results Exosomes derived from hUC-MSCs had typical morphology and specific markers.qRT-PCR results showed that, the relative expression quantity of M1 macrophages phenotypic molecular nitric oxide synthase 2 (NOS2) mRNA and inflammatory factor tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) mRNA in the lachrymal organization in the dry eye model group was significantly higher than those in the normal control group (3.06±1.00 vs. 1.00±0.03, 2.77±0.72 vs. 1.01±0.02 and 1.30±0.08 vs. 1.01±0.01, respectively), the relative expression quantity of M2 macrophages phenotypic molecular arginase 1 (Arg1), CD206 and IL-10 mRNA in the lachrymal organization in the dry eye model group was significantly lower than those in the normal control group (0.55±0.07 vs. 1.00±0.00, 0.60±0.13 vs.1.00±0.00, 0.65±0.14 vs. 1.01±0.01, respectively), with significant differences between them (all at P<0.05). In vitro, the relative expression quantity of M1 macrophages phenotypic molecular NOS2 mRNA and inflammatory factor TNF-α, IL-1β mRNA in PBMCs in the hUC-MSC-exo group was significantly lower than those in the PBS control group (0.59±0.08 vs.0.98±0.03, 0.56±0.07 vs. 1.03±0.11, 0.47±0.04 vs.1.00±0.08)(all at P<0.05); the relative expression quantity of M2 macrophages phenotypic molecular Arg1, CD206 mRNA and anti-inflammatory cytokine TGF-β, IL-10 and IL-4 mRNA in PBMCs in the hUC-MSC-exo group was significantly higher than those in the PBS control group (2.13±0.28 vs. 1.10±0.17, 1.32±0.03 vs. 1.01±0.06, 1.53±0.20 vs. 1.05±0.10, 1.47±0.08 vs.0.98±0.03, 1.51±0.16 vs. 1.01±0.03), with significant differences between them (all at P<0.05). Conclusions hUC-MSC-exo can polarize peripheral blood macrophages toward immune-suppressive M2-like phenotype, inhibit the production of pro-inflammatory cytokines TNF-α and IL-1β, and meanwhile increase the expression of anti-inflammatory factors IL-10 and TGF-β. Key words: Umbilical cord mesenchymal stem cells; Exosomes; Macrophages; Cytokines; Autoimmune dry eye

Analysis of different proteins in primary open angle glaucoma based on aqueous proteome

Objective To analyze the changes of protein expression in aqueous humor of patients with primary open angle glaucoma (POAG), and to explore the biological markers and potential therapeutic targets associated with disease occurrence. Methods A retrospective case-control study was adopted.Ten patients with age-related cataract and 10 patients with POAG combined with cataract.were collected at the Tianjin Medical University Eye Hospital from October 2016 to December 2017.In the process of surgery, 100 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access.Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry.The differential significance test was performed by Maxquant significances A. The differential proteins of the two groups were screened and determined with the conditions of P 2.The biological big data was annotated by the function of GO and KEGG.The study was approved by the Ethics Committee of the Tianjin Medical University Eye Hospital (No.2013KY[L]-10). Patients and their guardians all signed the informed consent. Results Ninty-seven differential proteins were detected in this proteomic analysis, including 48 up-regulated proteins and 49 down-regulated proteins.GO analysis significantly differs in protein function involved in many aspects, some different proteins including lipopolysaccharide-binding protein (LBP), cluster of Differentiation 163(CD163), C-reactive protein (CRP), annexin A1 (ANXA1) were involved in inflammation; redox-related proteins were glutathione S-transferase P (GSTP1), thioredoxin (TXN), some different proteins related with cell adhesion movement were cartilage oligomeric matrix protein (COMP), desmocollin-2 (DSC2) and laminin subunit beta-2 (LAMB2); procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1), solid protein (tenascin, TNC) are associated with fibrosis; some different proteins related to nerve growth were reelin (RELN), semaphorin-3F(SEMA3F), semaphorin-4B(SEMA4B). Metabolism-related proteins included pyruvate kinase (PKM), carb oxypeptidase N subunit 2 (CPN2) and so on.KEGG analysis indicated that the expression of NrF2/ERK signaling pathway and TGF-β/NF-κB signaling pathway were different between the two groups. Conclusions The expression of GSTP1 and TXN in the aqueous humor of POAG is significantly decreased, which may regulate cell adhesion and activity and expression of extracellular matrix by regulating NrF2/ERK1/2 and TGF-β/NF-κB signaling pathways.GSTP1 and TXN may serve as a potential biomarker and therapeutic target of POAG. Key words: Primary open angle glaucoma; Aqueous humor; Label free quantitative proteome; Glutathione S-transferase P; Thioredoxin; Transforming growth factor-β; nuclear factor-kappa B; Nuclear factor erythroid 2-related factor 2; extracellular regulated protein kinases

Proteomic analysis of aqueous humor in acute primary angle-closure glaucoma

Objective: To analyze the difference among expression of aqueous humor proteins in acute primary angle-closure glaucoma (APACG). Methods: Case-control study. The patients with APACG combined cataract (APACG with cataract group) and patients with cataract (cataract group), who had undertaken surgical treatment at the Tianjin Medical University Eye Hospital from October 2016 to June2017 were collected. Upon receipt of patient's consent, 50 μl of aqueous humor were collected with 1 ml syringe and No.1 needle through the surgical access during the surgery, and then injected into a sterile collection tube to be stored at -80 ℃. Those proteins extracted from aqueous humor were analyzed by quantitative proteomic mass spectrometry. The differential significance test was performed by Maxquant significances A approach. The differential proteins of the two groups were screened and determined with the conditions of P<0.05 and difference multiple>2. The functions and signal pathway of differential proteins in aqueous humor were annotated in biological big data, on the basis gene ontology (GO) and the Kyoto gene and genomic encyclopedia (KEGG) analyses. Results: There were 3 males and 7 females with an average age of (68±6) years in the APACG group. The cataract group included 2 males and 8 females with an average age of (71±8) years. There were no statistical differences in gender ratio and age between the two groups (both P>0.05). A total of 91 differential proteins were detected in this experiment, including 50 up-regulated proteins (annexinA1, vimentin, S100 calcium binding protein A8, interleukin 6, C reactive protein, laminin β2, etc.) and 41 down-regulated (keratin 85, γ-crystallin D, syntaxin-binding protein 5, semaphoring 4B, matrilin 2, cathepsin O, cadherin 4, semaphoring 3B, platelet-derived growth factor D, transforming growth factor β, etc.). On one hand, the functions of differential proteins involved in many aspects. AnnexinA1, CD163, S100 calcium-binding protein A8, C reactive protein, interleukin 6 are involved in the inflammatory reaction, cadherin 4 and laminin β2 regulate cell adhesion, matrilin 2, vimentin and laminin β2 participate in tissue fibrosis; on the other hand, KEGG analysis showed that the differential proteins participate diverse signaling pathways such as phosphatidylinositol-3-kinase-protein kinase B signaling pathway, transformation growth factor β signaling pathway, mitogen activated protein kinase signaling pathway, Toll-like receptor signaling pathway, the nuclear factor κ-light chain enhancer of the activated B cells signaling pathway, focal adhension and extracellular matrix receptor interaction pathway and so on. Conclusions: The expression of annexin A1 is significantly up-regulated in the aqueous humor in APACG, while some other factors such as transformation growth factor β, cadherin-4, and matrilin 2 are down-regulated. The change of proteins in aqueous humor is related with the outbreak of APACG. (Chin J Ophthalmol, 2019, 55: 687-694).

Clinical analysis of adult onset orbital xanthogranuloma

Objective: To investigate the clinical, imaging and pathological features of adult onset xanthogranuloma. Methods: Retrospective case series study.The clinical data of 4 adult patients with adult onset xanthogranuloma treated in the Tianjin Medical University Eye Hospital from 2015 to 2017 were analyzed. Results: There were 1 male and 3 females, aged 46-73 years, with an average age of 55 years. The duration of eyelid swelling was from 6 months to 6 years. One case was binocular and 3 cases were monocular. There were progressive enlargement of eyelid swelling and subcutaneous cord nodules with poor mobility and no tenderness in all 5 eyes. The eyelid skin in 2 patients (2 eyes) was bulging and yellow. CT examination showed swelling of the eyelids and soft tissue thickening in 5 eyes. There were lacrimal gland enlargement in 3 eyes, upper rectus muscle involvement in 3 eyes, external rectus muscle involvement in 1 eye, lower rectus muscle involvement in 1 eye, superior oblique muscle involvement in 1 eye, and involvement of both the superior and inferior rectus muscles in 1 eye. In 1 patient (1 eye), the lesion showed low and medium signals on T(1) weighted images and T(2) weighted images. Three patients (4 eyes) underwent color Doppler ultrasonography, showing the echo zone in the irregularly shaped eyelid was strong, the internal echo was uneven, the local echo was low, and the boundary was not clear. One of the eyes showed a blood flow signal. All patients underwent surgical resection. The pathological results showed infiltration of foamy tissue cells, Touton cells, lymphocytes and plasma cells. Immunohistochemistry demonstrated 3 patients (4 eyes) expressed CD68, and 1 patient (1 eye) expressed S-100. After 6 months to 2 years of follow-up, 3 patients had no recurrence. One patient developed eye discomfort at 6 months after surgery, and the symptoms were relieved after treatment with triamcinolone. Conclusions: Adult onset xanthogranuloma mainly manifest as eyelid swelling, periorbital mass and skin color changes, generally with no systemic involvement. Imaging examination mainly shows the involvement of soft tissues, lacrimal glands and muscles around the eyelids. The main features of the pathology are infiltration of foamy tissue cells, Touton giant cells, lymphocytes and plasma cells. (Chin J Ophthalmol, 2019, 55: 381-386).

The influence of two calculation methods on the outcomes of Toric intraocular lenses

Objective: To evaluate the influence of Barrett calculator and AcrySof calculator on astigmatism correction effect. Methods: This is a randomized prospective study. A total of 64 cases (81 eyes) who planed to undergo phacoemulsification at Tianjin Medical University Eye Hospital during January 2017 and March 2018 were enrolled and divided into two groups randomly, including of the Barrett calculator group of 34 cases (41 eyes) and the AcrySof calculator group of 30 cases (40 eyes). Preoperative ocular biological parameters were measured using Lenstar LS900. The Toric intraocular lenses (IOL) plans were determined based on Barrett calculator and the AcrySof calculator for the two groups respectively. Subjective optometry was performed by phoropter and Toric IOL alignment was detected by slitlamp examination at 1 and 3 months postoperatively. Statistical analysis was taken with the data of 29 cases (35 eyes) in the Barrett calculator group and 26 cases (35 eyes) in the AcrySof calculator group, there were 20 males (25 eyes) and 35 females (45 eyes) with an average age of (72±10) years. The difference between the predicted residual astigmatism by the two calculators and the residual astigmatism obtained by postoperative optometry is the error of refractive astigmatism (ERA). The magnitude error is the algebraic difference of ERA. Vector error(VE) is a vector difference of ERA. Statistical analysis of magnitude error and VE between the two groups were taken by student's t test or rank sum test. Results: At 1 months and 3 months, the magnitude error absolute value of Barrett calculator group were (0.19±0.16)D, (0.28±0.24)D, and those of AcrySof calculator group were (0.36±0.28)D, (0.46±0.41)D, and the differences were statistically significant (t=-3.050, -2.036, both P<0.05). At 1 month postoperatively, the overall, with-the-rule astigmatism, and against-the-rule astigmatism VE of the Barrett calculator group were (0.30±0.21)D, (0.26±0.22)D, (0.37±0.26)D respectively, and those of the AcrySof calculator group were (0.47±0.33)D, (0.51±0.34)D and (0.52±0.38)D respectively, the differences between the two groups were statistically significant (t=-2.533, -2.436, -2.150, all P<0.05). At 3 months postoperatively, the overall, with-the-rule astigmatism, and against-the-rule astigmatism VE of the Barrett calculator group were (0.37±0.28)D, (0.29±0.17)D, (0.35±0.27)D respectively, and those of the AcrySof calculator group were (0.59±0.46)D, (0.54±0.37)D, (0.64±0.52)D respectively, the differences between the two groups were statistically significant (t=-2.142, -2.038, -2.481, all P<0.05).The difference of X(EV) between the Barrett calculator group and the AcrySof calculator group was statistically significant[-0.13(-0.36-0.80)D vs. 0.19(-1.01-0.71)D, Z=-2.965,P<0.01], and the difference of Y(EV) was statistically significant [-0.02(-0.51-0.64)D vs. -0.15(-0.88-1.10)D, Z=-2.076, P<0.05] at 1 months. There was no significant difference in X(EV) and Y(EV) (both P>0.05) at 3 months. Conelusion: As compared to AcrySof Toric calculator, the application of Barrett calculator in selecting Toric IOL may reduce ERA and improve Toric IOL correction outcomes. (Chin J Ophthalmol, 2019, 55:208-213).

Synergism of mesenchymal stem cells and low-dose cyclosporine A on corneal allograft rejection

Objective To investigate the effect of mesenchymal stem cells (MSCs) combined with low-dose cyclosporin A (CsA) on corneal transplantation rejection and its mechanism. Methods A fully allogeneic rat cornea transplant model (Wistar rats to Lewis rats) was created.Thirty-six model rats were divided into MSCs group, CsA group and MSCs+ CsA group randomly by using the random number table method, with 12 rats for each group.In each group, six rats were used for the evalution of symptom observation and six for the assay of immune factor.Three days after corneal transplantation, slit lamp microscope was used to observe and record the vascularization, edema and opacity scores of corneal graft.After 18 days, spleen T helper cell(Th)1 and Th2 cytokines were measured by enzyme linked immunosorbent assay(ELISA). The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.This study protocol was approved by Ethic Committee of Tianjin Medical University Eye Hospital (No.TMUaMEC2017028). Results The survival time of corneal grafts in MSCs+ CsA group was prolonged in comparison with the MSCs group and CsA group, with significant differences between them([21.3±3.9]days vs. (14.8±2.4)days; [21.3±3.9]days vs.[16.0±1.1]days) (P=0.003, 0.004). Eighteen days after corneal transplantation, corneal opacity scores were 3.17±0.17, 3.00±0.00 and 2.17±0.17, corneal neovascularization scores were 2.67 ± 0.21, 2.33 ± 0.21 and 1.83 ± 0.21, respectively in the MSCs group, CsA group and MSCs+ CsA group, showing significant differences among the three groups (F=15.500, P<0.01; F=4.524, P=0.029). The corneal opacity scores and corneal neovascularization scores in the MSCs+ CsA group were significantly lower than those in the MSCs group and CsA group(all at P<0.05). Interleukin(IL)-2, IL-4, IL-10, and interferon-γ (IFN-γ) concentrations were all significantly different among the MSCs group, CsA group and MSCs+ CsA group (F=15.000, 12.810, 10.720, 17.960, all at P<0.01). Compared with the MSCs group and CsA group, Th1 subsets cytokines IFN-γ and IL-2 concentrations in the MSCs+ CsA group were significantly lower, and Th2 subsets cytokines IL-4 and IL-10 concentrations were significantly increased in the MSCs+ CsA group in comparison with the MSCs group and CsA group (all at P<0.05). Conclusions The combination of MSCs with low-dose CsA can effectively ameliorate immunological rejection by the modulation of the balance of Th1/Th2. Key words: Mesenchymal stem cells; Immunosuppressant; Corneal transplantation; Rejection

Clinical analysis of patients with orbital nonspecific inflammatory response diseases whose CT or MR images show enlargement of the infraorbital nerves

Objective: To discuss the clinical features, imaging features, pathological patterns, treatment principles and prognosis of the orbital nonspecific inflammatory response diseases patients whose CT or MR images show enlargement of the infraorbital nerves. Methods: A retrospective case series study. Seven orbital disease patients who were treated at Tianjin Medical University Eye Hospital between March 2013 and May 2017 were included. All patients, imaging pictures showed enlargement of the infraorbital nerve. The medical histories, clinical featuers, imaging features, pathologies, serological examinations, therapeutic processes and prognosis were collected and analyzed. Results: The 7 patients included 4 males and 3 females aged from 55 to 68 years (the average age was 60). Bilateral involvement was present in 5 of 7 patients. The main clinical manifestations include proptosis, increasing of orbital pressure, impairment of visual functions, reduction in ocular motility, facial sensation, periocular ache, involvement of lymph node and salivary gland, etc. CT results showed enlargement of infraorbital nerve, accompanied with or without the destruction of bone. The inflammatory response may involve with extraocular muscles and lacrimal glands, or were shown as lesions with irregular shape and blurred borders. The MR images generally showed equal T(1) and equal T(2) signal, accompanied with evident enlargement of the infraorbital nerve. Of all the 7 patients, 6 underwent operation, and the pathology confirmed that 2 of the 6 were involved with inflammatory pseudotumors and the rest 4 were involved with IgG4-related ophthalmic disease (IgG4-ROD). The level of IgG4 in the serum were detected for 4 patients, the results of 3 were high and the other was normal. Of all the 7 patients,1 patient underwent conservative treatment, but disease recurred for several times, and the serum IgG4 level for the patient was higher than normal;1 inflammatory pseudotumor patient was cured completely only by surgery, and has a favourable prognosis; 1 IgG4-ROD patient accepted glucocorticoid, surgery, radiotherapy and chemotherapy, but disease recurred several times; The rest of the patients accepted glucocorticoid and operation, 2 were sensitive to glucocorticoid, 2 were not sensitive, and 1 involved with recurrence. Conclusions: If orbital nonspecific inflammation response was accompanied with enlargement of infraorbital nerve, it is suggested that patient is more likely to be involved with IgG4-ROD;Pathology and serological tests can be used for the diagnosis of IgG4-ROD, however treatment effect appears to be poor for most patients, and patients prone to relapse. (Chin J Ophthalmol, 2018, 54: 515-519).

Preliminary investigation on embolization of orbital vascular malformation with medical glue injection intraoperatively

Objective: To summarize the treatment outcomes of embolizing orbital vascular malformation with intracavitary injection of medical glue during surgery. Methods: A retrospective case series study was performed on 25 patients with orbital vascular malformation who were treated at Tianjin Medical University Eye Hospital during March 2008 and March 2016. In the 25 patients(25 eyes), 7 were male and 18 were female. The range of age was 2-64 years and the median age was 29 years. The clinical features, operation records, pathological reports and follow-up data were analyzed. Results: The location of vascular malformation involved intraorbital in 11 cases and superficial area of eyelid and(or) face in 5 cases, as for the rest 9 cases, both intraorbital and superficial area were involved. Conjunctiva was involved in 4 patients. Clinical manifestation included intermittent protopsis or mass volumn changed (7 cases), pulsating exophthalmos and vascular murmur (1 case). Imaging examination showed solitary mass with regular shape in 5 cases and space occupying lesion with irregular shape and ill-defined margins in 20 cases. Optic nerve was involved in 7 cases. Surgical debulkling were performed via skin incision on the mass surface (in 3 cases), lateral orbitotomy (in 2 cases), and anterior orbitotomy (in 20 cases). The anterior orbitotomy approaches include skin incision under eyebrow (9 cases), skin incision under lower eyelid eyelash (3 cases), transconjunctiva joint lateral canthus incision (6 cases) and transconjunctiva incision only(2 cases). The intra-orbital part of vascular malformation involved intraconal compartment (10 cases) and extraconal compartment (10 cases). During the operation, vascular malformations were exposed and injected with medical aural and encephalic glue. The amount of injected glue ranged from 0.25 ml to 2.50 ml in divided doses. When the soft venous malformations turned hard, the lesions and remnant glue were fully removed. The whole procedure cause less bleeding and shorter time of operation. Histopathologic diagnosis were intraosseous hemangioma (1 case), arteriovenous malformation (2 cases), venous malformation (22 cases), including varix (4 case) and venous hemangioma (18 cases). One patient suffered from sudden central retinal artery embolism on the third day postoperatively, in which case, visual acuity recovered to 0.6 by timely rescue and appropriate procedure. Topical skin aseptic inflammation took place at the same side of medical glue injection in 3 cases which might be caused by medical glue. These 3 cases had superficial eyelid lesions. Postoperative follow up for patient was conducted from 6 months to 5 years. One young patient underwent recurrent orbital hematoma and many times surgery. Conclusions: Embolization of orbital vascular malformation with medical glue injection intraoperatively can be utilized as an easy approach to control hemorrhage. The surgeon should be careful with the application methods, for instance not to push too quickly, not to pass through the vascular malformation, and to remove the lesions and remnant glue completely, in order to avoid complications. (Chin J Ophthalmol, 2018, 54: 502-508).

The efficacy of conbercept or ranibizumab intravitreal injection combined with laser therapy for Coats\u2019 disease

PurposeThe current treatment approaches for Coats’ disease by intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents (ranibizumab or conbercept) combined with laser therapy were evaluated for the efficacy during the treatment.MethodsThe medical records of 28 patients diagnosed with Coats’ disease followed by the treatment with intravitreal injection of anti-VEGF agents and laser therapies at Tianjin Medical University Eye Hospital and Hebei Eye Hospital during July 2012 and October 2017 were reviewed retrospectively. Clinical outcomes were recorded with a minimum follow-up of 6 months. The patients were divided into ranibizumab- and conbercept-treated groups, as well as based on age: pediatric and adult groups.ResultTwenty-eight patients were involved in this study. The average number of the injections was 2.82 ± 0.98. Laser photocoagulation was conducted in all patients, and the average number of lasers was 2.63 ± 0.74. The average follow-up period was 24.29 ± 9.85 months. Fourteen patients (50%) were stable, 12 (43%) patients were improved, and 2 patients (7%) showed recurred subretinal fluid and exudation. The final best corrected visual acuity (BCVA) increased markedly after intravitreal injection of ranibizumab or conbercept combined with laser therapy (p = 0.029, p = 0.009, respectively). The number of injections and lasers between conbercept and ranibizumab groups did not vary significantly (p = 0.160, p = 0.573, respectively). Nine patients (60%) in the ranibizumab-treated group and five (38%) in the conbercept-treated group reached a stable phase, and five (33%) and seven (54%) patients got the vision improved after treated with ranibizumab or conbercept, respectively. In pediatric and adult groups, the initial and final BCVA differed significantly (p = 0.03, p = 0.008, respectively). However, the injection number was remarkably different (p = 0.02), while the laser numbers did not have any markedly difference (p = 0.38).ConclusionIntravitreal injection of ranibizumab or conbercept combined with laser therapy is an effective therapeutic option in Coats’ disease. Moreover, the intravitreal injection of ranibizumab or conbercept had no significant adverse effects and appeared to offer visual improvement in Coats’ disease.

WITHDRAWN: Associations between ten VEGF gene polymorphisms and susceptibility to type 2 diabetic retinopathy, proliferative diabetic retinopathy and nonproliferative diabetic retinopathy: a systematic review and meta-analysis

// Qianhui Yang 1 , Yan Zhang 1 , Xiandi Wang 2 , Xiaomin Zhang 1 and Xiaorong Li 1 1 Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute and Tianjin Medical University School of Optometry and Ophthalmology, Tianjin, China 2 Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, China Correspondence to: Xiaorong Li, email: lixiaorong@tmu.edu.cn Keywords : VEGF; gene polymorphism; diabetic retinopathy; meta-analysis Received : July 03, 2017 Accepted : December 27, 2017&nbsp;&nbsp;&nbsp;&nbsp; Epub: January 03, 2018&nbsp;&nbsp;&nbsp;&nbsp; Abstract The associations between VEGF gene polymorphisms and risk of type 2 DR, PDR and NPDR remian unclear. A systematic search and meta-analysis using OR with 95% CI was performed to evaluate the association. 26 studies containing 10 SNPs were analyzed. rs3025039 polymorphism was associated with DR risk in overall and Asian populations. rs2010963 was associated with increased of DR risk in overall populations and Caucasians. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. Significant associations were observed between rs3025021, rs13207351 and rs2146323 and DR risk in either overall populations, Caucasians or Asians. rs699947 and rs3025039 were associated with PDR risk in overall and Asian populations. rs1570360, rs3025039 and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039 and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR and NPDR.

Changes in the anterior cornea during the early stages of severe myopia prior to and following LASIK, as detected by confocal microscopy.

The present study aimed to assess the microscopic changes of the epithelium and Bowman's layer under confocal microscopy during the early stages of severe myopia following laser in situ keratomileusis (LASIK). The study comprised 54 patients (54 eyes) with severe myopia and 65 patients (65 eyes) with low and moderate myopia, who underwent LASIK surgery at Tianjin Medical University Eye Hospital (Tianjin, China). In all patients, the epithelium, Bowman's layer and anterior stroma were examined prior to and 1, 7, 30, 90 and 180 days after the surgery, using in vivo confocal microscopy. Six (6 eyes) of the 54 patients with severe myopia (11.1%) exhibited corneal epithelial changes following the surgery, as examined by a slit lamp. Three patients (3 eyes) exhibited epithelial changes under confocal microscopy. In 40 eyes (74.1%) with severe myopia, brown yellow changes were observed at the epithelial layer and in the central part of the cornea 6 months after the surgery; the same was observed in 35 eyes (53.8%) with low and moderate myopia. Microfolds in the Bowman's layer of eyes with severe myopia were detected in 48 eyes (88.9%), and in 54 eyes (100.0%) in the anterior stroma following LASIK, whereas microfolds were observed in 51 (78.5%) and 65 eyes (100%), respectively, in patients with low to moderate myopia. In the severe myopia group, 54 eyes (100%) exhibited nerve fibers below the epithelium that were detectable 1 day post-surgery; in 16 eyes (29.6%), 1 or 2 sub-epithelial nerve fibers were detected 7 days after the surgery, and in 24 eyes (44.4%), 1 or 2 sub-epithelial nerve fibers were observed 6 months after the surgery. In eyes with low and moderate myopia, the figures were 100, 38.5 and 64.8%, respectively. The nerves of neither group returned to the pre-operative level. In conclusion, neurotrophic epitheliopathy, microfolds in Bowman's layer and anterior stroma were detected in the present patients with severe myopia of the cornea following LASIK, and the recovery of nerve fibers required an extended period of time.

Morphological evalution of obstructive meibomian gland dysfunction by noninvasive Keratograph

Background Obstructive meibomian gland dysfunction (OMGD) is due to the meibomian gland duct obstruction and/or meibum abnormal secretion.Meibomian gland morphological change is important to clinical observation. Objective This study aimed to image the meibomian gland structures and the morphological changes in eyes with OMGD using a non-contact infrared meibography system (Keratograph 5M). Methods A case-control study was performed in Tianjin Medical University Eye Hospital from January to June in 2015.Sixty OMGD patients and 60 age-matched healthy controls were recruited.Ocular Surface Disease Index (OSDI) questionnaire was employed for the assess of ocular surface symptoms, and slit-lamp examination was performed for the observation of lid margin and meibomian gland orifices.Meibomian gland secretion scores and Keratograph 5M examination the morphological changes of the meibomian glands.According to OSDI questionnaire, the patients of OMGD were classified into mild group (12.0 2/3 of the total meibomian gland area). Written informed consent was obtained from all subjects before the examination. Results The OSDI, meibomian gland orifices, meibomian gland secretion scores and meibomian gland dropout scores were significantly higher, and BUT was dramatically shorter in the OMGD group than those in the normal group, showing significant differences between the two groups (Z=-9.425, -8.954, -7.781, all at P<0.05). The BUT was (6.10±1.91)s and (10.67±2.11)s, and meibomian gland dropout scores were 1.35±0.90 and 0.88±0.64 in the OMGD group and normal control group, showing significant differences between the two groups (t=3.276, -12.418, both at P<0.05). OSDI, meibomian gland secretion scores and meibomian gland dropout scores were significantly in three intergroups (H=52.121, 13.642, 37.180, all at P<0.05). BUT, meibomian gland orifices were significantly different among the mild, moderate and severe OMGD (F=58.191, 8.474, both at P<0.05). OSDI showed a significantly high positive correlation with meibomian gland orifices, meibomian gland secretion scores and meibomian gland dropout scores (r=0.708, P=0.000; r=0.759, P=0.000; r=0.270, P=0.003). BUT showed negative correlation with meibomian parameters (r=-0.692, P=0.000; r=-0.691, P=0.000; r=-0.192, P=0.036). Conclusions Keratograph 5M provides an effective noninvasive method in assessing the image of the meibomian gland structures and meibomian gland dropout.There are differences in the ocular surface and meibomian glands between the OMGD patients and normal persons. Key words: Meibomian gland dysfunction; Meibomian gland dropout; Ocular surface disease index; Keratograph 5M

Comparison of safety and generalizability between day surgery and traditional surgey for cataract

Objective To explore if the day surgery for cataract is safe and should be popularized. Methods From September to October in 2015, among the patients who received the ultrasonic phacoemulsification and intraocular lens implantation in the cataract department of Tianjin Medical University Eye Hospital, according to the admission time, one hundred and three patients were chosen respectively from the day ward (the experimental group) and the traditional ward (the control group) based on the purposive sampling. The average time of waiting for admission, the falls events before admission, the awareness about postoperative considerations, the postoperative complications and the infection rate between the two groups were compared. Results The average time of waiting for admission in the experimental group was much shorter than that in the control group, (6.36±4.02) days vs. (21.35±18.58) days. The difference was significant (Z= -8.386, P<0.01). The rate of falls before admission in the experimental group was lower than that in the control group and the difference was significant, 9.71%(10/103) vs. 20.39% (21/103), χ2=4.595, P <0.05. No infection happened in both groups. Conclusions The day surgery model doesn′t increase the risk and is as safe as the traditional surgery model. It should be extended as it also has the advantages of shorter hospital stay, less medical resource consumption and less hospitalization expenses, besides, it saves time and labor. What′s more, the mean waiting time for hospitalization for day surgery is shorter. It means the patients can receive the operation as soon as possible, which ensures the patients′ safety, and reduce the unsafe factor in their life, bring the benefit to the society. Key words: Cataract; Complications; Day surgery

Primary culture and morphological characteristics of human lacrimal adenoid cystic carcinoma cells

To explore a method of primary culturing human adenoid cystic carcinoma cells of lacrimal gland. Experiment research. Tumor tissue was obtained from the surgical material of a patient diagnosed as lacrimal adenoid cystic carcinoma in Tianjin Medical University Eye Hospital during May 16th to June 1st.We gained primary cells via tissue culture techniques. Mixed cells were removed through several ways.Observed cell morphological characteristics by phase contrast microscope, scanning electron microscope and transmission electron microscope. Cyto-immunochemical staining was applied to detect the expressions of vimentin, desmin, S-100, cytokeratin, pan and CD34. Their expressions were also detected in the tumor tissue except CD34. Made cell growth curve and calculated cell doubling time. The outgrowth of cells was observed by day 5 after seeding tissues, and then cells generated slowly. The first passage proceeded by day 32, and the classical epithelioid cell colonies was observed by day 69 after inoculation. Purified cells of human lacrimal adenoid cystic carcinoma were obtained after the removal of mixed cells through several ways, which have been successfully subcultured for more than 100 passages. The 25th passage LACC cells appeared to be typically epithelioid cells, they showed contact inhibition as the density high enough.SEM and TEM showed the 25th passage LACC cells were malignant tumor cells poorly differentiated. They showed positive reaction with vimentin, cytokeratin (pan) as well as S-100, but negative reaction with desmin and CD34, which were consistent with the tumor tissue. The cell growth curve turned like a sigmoid one, and the cell doubling time was 37.1 h. We gained purified LACC cells, and understood the morphological characteristics, laying the foundation for the establishment of a human lacrimal adenoid cystic carcinoma cell line.