1.Analysis of differentially expressed genes and metabolic pathways in human uveal melanoma
Kuifang, DU ; Xiaolin, XU ; Yang, LI ; Yingzhi, WANG ; Wenbin, WEI
Chinese Journal of Experimental Ophthalmology 2015;33(11):996-1003
Background Studies showed that there exsits differential gene expression in human uveal melanoma (UM).However, the researching results are somewhat inconsistently abroad, while relevant literature is still less in China.Few domestic researches have reported the abnormalities of gene transcription level or the pathways of these genes.Objective This study was to compare the gene expression profiles between human UM and normal uvea tissues and analyze the metabolic pathways involved in these differentially expressed genes.Methods Four human UM samples were collected in Beijing Tongren Eye Center,and 4 pieces of normal uveal tissues from 4 donors served as controls.The expression of genes was detected with Human Genome U133 Plus 2.0 chip,and the expression profiles were compared between two groups.The biological functions and active pathways of the genes were analyzed by Gene Ontology Enrichment Analysis Software Toolkit (GOEAST).Results Compared with the normal controls,4 165 differential genes were screened in human UM (12.50%) ,including 1 236 up-regulated genes (3.71%) and 2 929 down-regulated genes (8.79%) ,in which the genes of raised more than 5-, 10-,50-and 100-fold were 113,21,1 and 1, respectively, and the genes of reduced by 50% ,90% ,98% and 99% were 1 053,422,33 and 5,respectively.The functions of these differentially expressed genes were associated with cellular differentiation and growth,development, cell adhension, immun response, transcriptional contol, signal transduction and anti-apoptosis.The metabolic pathways of differentially expressed genes included angiogenesis pathway, cell-cycle related protein kinase pathway and immune regulatory pathway (involving B lymphocytes and T lymphocytes).ConclusionsGene expression profiles are evidently different between human UM and normal uveal tissue.The variation of the gene profiles in human UM leads to the changes of multiple biological functions including angiogenesis and kinase pathway even immun system.It is implied that the pathogenesis of human UM is a comprehensive effect of multiple genes and biological pathways.
2.Clinical manifestation and treatment of ocular immune reconstitution inflammatory response syndrome in acquired immunodeficiency syndrome patients with cytomegalovirus retinitis
Wenjun KONG ; Wenbin WEI ; Lianyong XIE ; Chao CHEN ; Kuifang DU
Chinese Journal of Experimental Ophthalmology 2021;39(7):626-631
Objective:To investigate the ocular characteristics and treatment prognosis of ocular immune reconstruction inflammatory syndrome (IRIS) in patients with cytomegalovirus retinitis (CMVR) complicated with acquired immunodeficiency syndrome (AIDS).Methods:A serial case-observational study was conducted.Seventeen eyes from 15 male 21-to 43-year-old AIDS patients combined with CMVR, who were diagnosed with IRIS at Beijing You'an Hospital, Capital Medical University from February 2016 to December 2018 were included.The best corrected visual acuity (BCVA) of patients was recorded, and the intraocular pressure and anterior segment was measured with a non-contact tonometer and a slit-lamp microscope, respectively.The ocular fundus was observed by fundus photography and optical coherence tomography (OCT). Reverse transcription polymerase chain reaction was used to measure the cytomegalovirus deoxyribonucleic acid (CMV-DNA) content in the aqueous humor during the occurrence of IRIS.The flow cytometry was employed to determine the peripheral blood CD4 + T lymphocyte count before highly active antiretroviral therapy (HAART) and during the occurrence of IRIS.All patients were followed for 3 to 25 months, with an average of 15 months.The HAART time of patients was 17 to 104 days, with an average of (66.1±27.4) days.Patients with anterior segment inflammatory reactions were given the anti-inflammatory and mydriatic treatment.Patients with severe vitreous opacity were intravitreally injected with 4 mg of triamcinolone.Patients with macular edema were given 0.5 mg intravitreal injection of conbercept.The study adhered to the Declaration of Helsinki and was approved by an Ethics Committee of Beijing You'an Hospital, Capital Medical University (No.[2017]11). Written informed consent was obtained from each patient prior to any examination. Results:Anterior segment inflammation (Tyndall effect, KP, post-iris adhesion) was found in 9 eyes, vitreous opacities to varying degrees in 11 eyes, and macular edema in 2 eyes.The CMV-DNA content was negative (<500 copies/ml) in 15 eyes.The CD4 + T lymphocyte count in peripheral blood during IRIS was 67 (51, 99) cells/μl, which was significantly higher than 17(6, 20) cells/μl before HAART treatment ( Z=-4.48, P<0.01). Two of the 15 AIDS patients had tuberculosis.The BCVA of the patients was improved from 0.30 (0.10, 0.55) before treatment to 0.50 (0.35, 0.60) after treatment, and the difference was statistically significant ( Z=-2.34, P=0.019). Conclusions:The anterior and posterior segment may be involved in IRIS patients with AIDS and CMVR, and the corresponding ocular treatment is effective.
3.Analysis of ultra-wide-field fundus manifestations of cytomegalovirus retinitis in acquired immunodeficiency syndrome patients
Kuifang DU ; Xiaojie HUANG ; Chao CHEN ; Wenjun KONG ; Lianyong XIE ; Wenbin WEI
Chinese Journal of Ocular Fundus Diseases 2020;36(9):669-674
Objective:To observe the ultra-wide-angle fundus imaging characteristics of acquired immunodeficiency syndrome (AIDS) combined with cytomegalovirus retinitis (CMVR).Methods:This study was a retrospective study. From July 2017 to November 2019, 124 eyes of 86 patients diagnosed with AIDS and CMVR at the Department of Ophthalmology, Beijing You'an Hospital, Capital Medical University, were included in the study. Among them, 80 patients were males (93.0%) and 6 patients were females (7.0%) with 17-58 years old. The average age was (36.86±8.82) years old. There were 48 cases (55.8%) in one eye and 38 cases (44.2%) in both eyes. All the affected eyes underwent indirect ophthalmoscope fundus examination and Aalborg ultra-wide-angle fundus photography examination. According to the characteristics of CMVR in ultra-wide-angle fundus images, it can be divided into classic type, granular type, frost-like dendritic vasculitis and optic neuroretinitis. We observed and analyzed the type of fundus of the affected eye. According to the position of the vortex vein in the fundus image and record of the lesion as the posterior pole or peripheral part, the scope of the lesion was divided into ≤1 quadrant, >1 quadrant and ≤2 quadrants (1-2 quadrants), >2 quadrants and ≤3 quadrants (2-3 quadrants), >3 and ≤4 quadrants (3-4 quadrants). The upper and lower vascular arches or disc edges of the macula were used as boundaries to record whether the macular area or optic disc was involved. At the same time, we recorded whether the vitreous body had obvious turbidity. The comparison of CD4 + T lymphocyte count between patients of different types was performed by one-way analysis of variance, and the comparison of the positive rate of blood CMV-DNA was performed by the χ2 test; pairwise comparisons between groups were performed by the least significant difference method. Results:Among the 124 eyes, CMVR was classified into 35 eyes (28.2%) with classic type, 68 eyes with granular type (54.8%), 3 eyes with frost-like dendritic vasculitis (2.4%), and 18 eyes with optic neuroretinitis (14.5%). The lesion involved 83 eyes (66.9%) at both the posterior pole and the periphery, 22 eyes (17.7%) confined to the posterior pole, and 19 eyes (15.3%) confined to the periphery; the extent of the lesion was ≤1 quadrant in 76 eyes (61.3%), 23 eyes (18.5%) in 1-2 quadrants, 7 eyes (5.6%) in 2-3 quadrants, and 18 eyes (14.5%) in 3-4 quadrants. 54 eyes (43.5%) showed lesions involving the macular area; 52 eyes (41.9%) had lesions involving the optic disc; 33 eyes (26.6%) showed obvious vitreous inflammatory opacities. Among 86 patients, the average number of CD4 + T lymphocytes in 82 patients was 1 to 168 cells/μl, with an average of 33.60±40.02 cells/μl; the remaining 4 patients (4.7%) were unknown. There was no statistically significant difference in the positive rate of CD4 + T lymphocyte count and blood CMV-DNA load between patients in different subtypes groups ( F=0.863, 0.926; P=0.462, 0.431). Conclusion:The ultra-wide-angle fundus images of AIDS combined with CMVR have certain characteristics, which can manifest as classic, granular, frost-like dendritic vasculitis and optic neuroretinitis.
4.Clinical manifestations of the initial-stage cytomegalovirus retinitis in acquired immunodeficiency syndrome patients
Kuifang DU ; Xiaojie HUANG ; Chao CHEN ; Wenjun KONG ; Lianyong XIE ; Wenbin WEI
Chinese Journal of Ocular Fundus Diseases 2021;37(7):513-517
Objective:To investigate the clinical manifestations of acquired immunodeficiency syndrome(AIDS) patients with initial-stage cytomegalovirus (CMV) retinitis (CMVR).Methods:Retrospective case series study. From July 2017 to November 2019, 21 patients with 22 eyes of AIDS combined with CMVR in the initial stage of AIDS and CMVR diagnosed in the eye examination in the study. Among them, there were 19 males with 19 eyes and 2 females with 3 eyes; the average age was 34.3±9.6 years. The average CD4 + T lymphocyte count of patients was 26.1±23.2/μl. Routine fundus screening revealed 17 cases, and the contralateral eye disease was found in 4 cases. There were 13 cases of CMVR in both eyes (61.9%, 13/21). Among them, both eyes were in the initial stage of CMVR, and the contralateral eyes were in the early stage of CMVR in 12 cases. The contralateral eye included 2 cases of human immunodeficiency virus-related retinal microangiopathy, 1 case of optic disc edema, and 5 cases of no obvious abnormality on fundus examination. All patients underwent slit lamp microscopy and ultra-wide-angle fundus photography examination. At the same time, 18 eyes underwent optical coherence tomography (OCT). Blood CMV-DNA detection was performed in 17 cases within 1 week before the first diagnosis; aqueous CMV-DNA detection was performed in 7 eyes within 1 week after the first diagnosis. Within 1 week after the fundus examination, 8 eyes of 8 cases and 8 eyes of 7 cases were received and not received systemic anti-CMV treatment; the treatment status was unknown in 6 cases and 6 eyes. After treatment, 18 eyes of 17 cases were followed up. The follow-up time was 0.5-28 months. Results:There were no obvious abnormalities in the anterior segment examination of all the affected eyes; the vitreous body was transparent. The fundus lesions were less than 1 optic disc diameter (DD), and they were white granular, clustered, with blurred edges. Among them, there were granular satellite lesions around the lesion in 18 eyes (81.8%, 18/22). The lesions were located in 19 eyes (86.4%, 19/22) in zone 2, 1 eye in zone 1 and 2 (4.5%, 1/22), and 2 eyes in zone 3 (9.1%, 2/22). In 18 eyes that underwent OCT examination, 12 eyes failed to obtain image data because the lesion was not in the conventional scanning range; the other 6 eyes showed the inner or full retina thickened or atrophy depression, structural destruction, accompanied by local vitreous punctate strong reflection. Among the 17 patients who underwent blood CMV-DNA testing, 1 (5.9%, 1/17) and 16 (94.1%, 16/17) cases were CMV-DNA negative and positive, respectively. The 7 eyes that underwent the CMV-DNA test of aqueous humor were all negative. Among the 18 eyes who were followed up, the lesions did not expand, and gradually subsided and absorbed in 4 eyes (22.2%, 4/18); the varying degrees of lesion enlargement in 14 eyes (77.8%, 14/18).Conclusion:The patients with AIDS and CMVR at the initial stage have no obvious ocular symptoms; the fundus shows white granular lesions less than 1 DD with blurred edges.