Objective To observe the therapeutic effects of ganciclovir (GCV) with different injection methods on experimental acute retinal necrosis (ARN). Methods The right eyes of 41 pigmented rabbits were infected by herpes simplex virus (HSV-1) (COS strain) to establish ARN animal model. After 24 and 72 hours, GCV was given by intravitreal injection (10 eyes), intravenous injection (11 eyes) and the intravitreal+intravenous injection (10 eyes); intravitreal injection of GCV and dexamethasone (6 eyes) was also included. Four eyes were not treated as the control. The dosage of GCV in intravitreal and intravenous injection was 800mu;g and 5mg/kg weight, respectively. Retina necrosis was observed and the grade was recorded 1-21 days after injection according to the grade standard of retinopathy. The maximum grades of retinal necrosis in different groups were compared. Results The grade of retinal necosis was 3.8 in the control group, and 0.2, 0.4, 0.8, and 2.2 in intravitreal injection, intravitreal+intravenous injection, intravitreal injection with GCV and dexamethasone, and intravenous injection, respectively, 24 hours after the model was set up. The effects of the first 3 groups were obviously better than the last group (P=0.003, 0.011, 0.045); while the difference among the first 3 groups were not significant (P=0.881、0.054、0.107). Seventy-two hours after the model was set up, the grades of retinal necrosis were above 1.4 in 4 groups, and the differences among the 4 groups were not apparent (P=0.214). Conclusions In the animal model of ARN, intravitreal injection with GCV can effectively decrease the grade of retinal necrosis. The difference among intravitreal injection, intravitreal+intravenous injection, intravitreal injection with GCV and dexamethasone, and intravenous injection is not significant.
目的 比较更昔洛韦联合甲泼尼龙综合疗法和甲泼尼龙综合疗法治疗病毒性视神经炎的疗效。 方法 将2008年10月－2010年3月入院41例（60只眼）病毒抗体检测阳性的病毒性视神经炎患者随机分为治疗组，21例30只眼）和对照组（20例30只眼）。于治疗前和治疗第3、7、14、30、90、180天观察两组患者的视力、视野。 结果 两组患者的视力、平均视野缺损治疗组采用更昔洛韦联合甲泼尼龙综合疗法，对照组采用甲泼尼龙综合疗法。均随时间得到改善（P＜0.001）。两组患者视力在治疗的第3天开始恢复，30 d治疗组视力明显优于对照组（P＜0.05），治疗180 d时两组视力改善无差异（P＞0.05）；治疗组与对照组分别在第7天和第14天平均视野缺损开始恢复（P＜0.001）。 结论 更昔洛韦联合甲泼尼龙综合疗法较单纯甲泼尼龙综合疗法治疗病毒性视神经炎能更快提高患者视力、恢复视野、改善患者视觉质量。
ObjectiveTo evaluate the efficacy and safety of reduced-dose intravitreal ganciclovir for the treatment of acquired immunodeficiency syndrome (AIDS) patients with cytomegalovirus retinitis (CMVR).MethodsA prospective observational cohort study observed 15 AIDS patients (28 eyes) who suffered from CMVR onset between January 2016 and December 2018 at Nanning Aier Eye Hospital. Among this 28 eyes, BCVA of 6 eyes (21.4%) were between moving hand to counting finger, 15 eyes (53.6%) were between 0.02 to 0.1 and 7 eyes were better than 0.1 (25.0%). All eyes received intravitreal injection 0.1 ml of ganciclovir at 4 mg/ml (contain ganciclovir 0.4 mg). The induction regimen was twice weekly for 2 weeks and a maintenance period of the same dose weekly. The mean number of injections was 7.1±1.7 times. For hospitalized patients who had no contraindicated received a 14-day twice daily intravenous ganciclovir (IVG) 5.0 mg/kg·d until complete resolution of CMVR. All patients were divided into intravitreal ganciclovir (IVTG) group and IVTG+IVG group according to different treatment plans, which were 5 cases with 8 eyes and 10 cases with 20 eyes, respectively. The follow-up was more than 6 months. BCVA, complete resolution or stable of the lesion and complications were observed.ResultsSix months later, 20 eyes (71.4%) had a obvious reduced or disappeared of the anterior chamber and vitreous inflammation, and the retinal lesions became stable or complete resolution. 24 eyes showed improvements of BCVA and 4 eyes showed stable. 2 eyes (7.1%) presented with BCVA ≤ counting finger, 7 eyes (25.0%) were 0.02 - 0.1 and 19 eyes were ≥ 0.1 (67.9%). Compared with before treatment, the ratio of BCVA that less than or equal to counting finger and between 0.02 to 0.1 decreased (21.4% vs 7.1% and 53.6% vs 25.0%, respectively), but the ratio of BCVA better than 0.1 increased (25.0% vs 67.9%). When IVTG+IVG group was compared with IVTG group, the average time-to-resolution of CMVR were 83.2±25.2 and 85.3±24.4 days respectively. There was no significant difference in resolution times (Z=0.17, P=0.87). The ratio of retinal lesions became stable or complete resolution were 75.0% (15 eyes) and 62.5% (5 eyes), there was no evident difference in time-to-resolution between the two groups (F=0.42, P=0.51). No recurrence was seen during the follow-up period. In cases of unilateral CMVR, there were no patients with a second eye involvement during the follow-up period. No endophthalmitis, vitreous hemorrhage, retinal detachment were found in our study.ConclusionReduced-dose intravitreal ganciclovir is a safe and effective treatment option for CMVR.
【摘要】 目的 探讨儿童传染性单核细胞增多症（IM）的临床特点。 方法 回顾性分析2005年8月-2009年8月收治的151例IM患儿的症状、体征、实验室检查及治疗效果。 结果 IM临床表现以发热、咽峡炎、肝脾和淋巴结肿大最常见，鼻塞、眼睑浮肿也是重要体征。外周血出现异型淋巴细胞及EBV-IgM抗体检测可帮助确诊。更昔洛韦治疗IM效果确切。 结论 应重视IM临床特点，有助于早期诊断并提高确诊率，应用更昔洛韦治疗值得推广。【Abstract】 Objective To investigate the clinical features of infectious mononucleosis (IM) in children. Methods A total of 151 children with infectious mononucleosis admitted from August 2005 to August 2009 were reviewed. The symptoms, signs, laboratory tests, and treatment of infectious mononucleosis were analyzed. Results Fever, angina, hepatomegaly, splenomegaly, and swollen lymph nodes were the most common clinical manifestations of IM. Nasal congestion and eyelid edema were also two important signs. Atypical lymphocytes in peripheral blood and EBV antibody (VCA-IgM) could help confirm the diagnosis. The antiviral treatment with ganciclovir was effective for infectious mononucleosis. Conclusion Clinical features of infectious mononucleosis are helpful to the diagnosis. Treatment with ganciclovir should be promoted.
ObjectiveTo evaluate the therapeutic effect of liver transplantation (LT) combined with adenovirus-mediated delivery of herpes simplex virus thymidine kinase / ganciclovir (ADV-TK/GCV) in treatment of patients with hepatocellular carcinoma (HCC), so as to benefit more patients with HCC beyond the Milan criteria. MethodsThe clinicopathologic data of patients with HCC underwent LT by the author team since 2007 were collected and analyzed. The patients were assigned into simple LT group and LT+ADV-TK/GCV group. The 5-year cumulative overall survival rate and relapse free survival rate of all LT patients and the patients with LT beyond the Milan criteria by simple LT and LT+ADV-TK/GCV therapy were compared. Meanwhile, Cox regression was used to analyze the risk factors affecting long-term overall survival rate and relapse free survival rate of all patients with HCC after LT. ResultsA total of 216 patients eligible for inclusion were collected in this study, including 134 patients in the simple LT group and 82 patients in the LT+ADV-TK/GCV group, 162 of whom beyond the Milan criteria, including 101 patients underwent the simple LT and 61 patients underwent the LT+ADV-TK/GCV. There were no statistical differences in the baseline data between the simple LT and LT+ADV-TK/GCV in all patients and patients beyond the Milan criteria (P>0.05). There were no statistical differences in 5-year overall survival rate and relapse free survival rate of all patients with HCC (P>0.05). The 5-year cumulative overall survival rate of the LT+ADV-TK/GCV group was better than that of the simple LT group in the patients beyond the Milan criteria (χ2=4.11, P=0.047), but it was not found that the 5-year cumulative relapse free survival rate had statistical difference (27-month survival time as the critical value, P=0.46, P=0.06). Cox regression multivariate analysis results showed that the larger cumulative tumor diameter, the preoperative elevated serum alpha fetoprotein (>400 μg/L), later TNM stage, and without combination of ADV-TK/GCV therapy increased the probability of shorter overall survival of patients after LT; and the patient’s older age, the larger cumulative tumor diameter, and later TNM stage increased the probability of shorter relapse free survival after LT, and it was not found that the combination of ADV-TK/GCV therapy had an impact on the relapse free survival. ConclusionLT combined with ADV-TK/GCV therapy can obviously improve overall survival among patients beyond the Milan criteria, more patients with advanced HCC will be candidates for LT combined with ADV-TK/GCV therapy.
ObjectiveTo observe the changes of varicella zoster virus (VZV)-DNA load in aqueous humour samples in VZV-induced acute retinal necrosis (ARN) in the early stages of antiviral treatment. MethodsA retrospective observational clinical study. From April 2016 to April 2018, 24 patients with 24 eyes of VZV-induced ARN who were diagnosed by Department of Ophthalmology, Eye and ENT Hospital of Fudan University and received complete aqueous humor sampling were included in the study. Among them, there were 13 males with 13 eyes, 11 females with 11 eyes; 12 left eyes and 12 right eyes; the age was 52.0±9.5 years old (39-71 years old). The time from the onset of ocular symptoms to the diagnosis of ARN was 16.6±6.1 days (7-30 days). Best-corrected visual acuity (BCVA) and ultra-wide-field fundus imaging were performed in all affected eyes. The BCVA examination was carried out using the Snellen visual acuity chart, which was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity. All patients were given intravitreal injection of 40 mg/ml ganciclovir 0.1 ml (including 4 mg of ganciclovir), 2 times a week, until the active necrotizing retinal lesions subsided, at most after the diagnosis 4 weeks, with a maximum of 9 injections. The follow-up period was 12.8±5.6 months. The aqueous humor samples were collected at presentation and 4, 7, 14, 21, 28 days after the initiation of antiviral therapy, and the VZV-DNA load was detected by real-time quantitative polymerase chain reaction. A plateau phase and a logarithmic reduction phase of the DNA load changes were observed after antiviral treatment began. Wilcoxon rank sum test was used to compare and analyze the differences in BCVA between the eyes at baseline and last follow-up. ResultsThe mean viral load at presentation was 8.6×107±1.3×108 copies/ml. The initial plateau phase last for an average of 7.4±2.4 days. In the following logarithmic reduction phase, the mean slope of the decline in viral load was －0.13±0.04 log/day, and the expected time for half reduction of the initial viral load was 2.5±0.7 days. After 28 days antiviral treatment, the viral load decreased to 1.7×105±1.8×105 copies/ml. In the course of the disease, rhegmatogenous retinal detachment occurred in 16 eyes. Before treatment and at the last follow-up, the logMAR BCVA of the affected eye was 1.1±0.6 and 0.8±0.7, respectively. The results of correlation analysis showed that the logMAR BCVA at the last follow-up was correlated with the initial VZV-DNA load (r=0.467, P=0.033). ConclusionThe VZV-DNA load in the aqueous humor of eyes with VZV-induced ARN is significantly decreased after antiviral treatment, which is closely related to the clinical process of ARN.
ObjectiveTo explore safe dosage of single intravitreal injection of ganciclovir (IVG) in healthy rabit eyes, and to explore retinal toxicity of different dosage of ganciclovir after continues intravitreal injection into the vitreous cavity of healthy albino rabbit eyes. MethodsTen healthy New Zealand albino rabbits were divided into 5 groups with 2 rabbits in each group. Each group was injected with 1 mg/0.025 ml, 2 mg/0.025 ml, 5 mg/0.025 ml, 10 mg/0.025 ml ganciclovir or 0.025 ml saline (control group). After 1 week of intervention, rabbits were examined by ultra-wide-angle fundus photography, optical coherence tomography (OCT) and full field electroretinogram (ERG). The maximum mixed response of rod and cone cells (Max-R) was measured under dark adaption conditions, cone response (Cone-R) and 30 Hz flicker response (30 Hz-R) were measured under light adaption conditions. Twenty-four healthy New Zealand albino rabbits were randomly divided into a low-dose experimental group, a low-dose control group, a high-dose experimental group, and a high-dose control group, with 6 rabbits in each group, with the right eye as the experimental eye. The rabbits in the high-dose experimental group were continuously injected with ganciclovir 2 mg/0.025 ml, once a week, for a total of 4 times. The rabbits in the low-dose experimental group were injected with 1 mg/0.025 ml ganciclovir, the induction period was 2 times/week, a total of 4 times; the maintenance period was 1 time/week, a total of 2 times. The rabbits in the high-dose control group and the low-dose control group were injected with 0.025 ml normal saline into the vitreous cavity respectively. Full-field ERG examination was performed 1 day before each injection and 1 week after the last injection. Max-R was measured under dark-adapted conditions, and Cone-R and 30 Hz-R were measured under light-adapted conditions. OCT was recorded before the first injection and one week after the last injection. One week after the last injection, the experimental rabbits in each group were sacrificed for hematoxylin-eosin staining, and the retinal structure was observed under a light microscope. The comparison of a-wave and b-wave amplitude of Max-R, Cone-R and 30 Hz-R amplitude at different time was performed by two independent sample nonparametric test. ResultsThere were no abnormal results of fundus photography, OCT and ERG after single intravitral injection of 1 mg or 2 mg ganciclovir. One week after single 5 mg IVG, fundus photography of rabbits showed vascular occlusion and preretinal hemorrhage and ERG showed slight decrease of amplitude of Max-R, Cone-R and 30 Hz-R. One week after single 10 mg IVG, retinal necrosis and exudative changes were also observed. OCT showed edema and unclear retinal structure in the necrotic area. ERG showed significant decrease of amplitude of Max-R, Cone-R and 30 Hz-R. After continuous IVG in high dose and low-dose experimental group, the amplitude of Max-R a wave (Z=－0.160, 0.000) and b wave (Z=－0.321, 0.000), Cone-R a wave (Z=－0.641,－0.641) and b wave (Z=－0.321, －0.160), and 30 Hz-R (Z=－0.321,－0.160) showed no difference compared to control group. No histologic evidences of retinal microstructure abnormalities were found in both groups. OCT and fundus photography before and after the intervention did not show any difference, either. ConclusionThere was no retinal toxicity of continuous 1 mg or 2 mg IVG recorded in albino rabbits.