Objective To evaluate the effectiveness and safety of foscarnet and ganciclovir for cytomegalovirus retinitis associated with acquired immune deficiency syndrome (AIDS). Methods We searched MEDLINE (1966 to 2005.12), EMBASE (1974 to Dec.2005), The Cochrane Library (Issue 4,2005), CBM (1978 to Dec.2005), CMCC (1994 to Dec. 2005), CNKI (1994 to Dec. 2005) and VIP (1989 to Dec. 2005). We identified randomized controlled trials of foscarnet versus ganciclovir. Two independent reviewers collected and evaluated details of study populations, interventions, and outcomes using a data extraction form. We conducted meta-analysis of the homoeonomous data. Result Three studies involving 451 patients were included. Meta-analysis showed foscarnet was better than ganciclovir with the following outcomes: mortality (RR=0.84, 95%CI 0.70 to 1.00, P=0.05); male genital ulcers (RR=1.29, 95%CI 0.60 to 2.82, P=0.002). There were no significant differences in ocular symptoms, relapses and other side effects. Conclusion Foscarnet in the treatment of cytomegalovirus retinitis in AIDS patients may be more benefical than ganciclovir with regard to mortality and male genital ulcers, but the supporting evidence is not very b because there are only three trials.
ObjectiveTo observe the image characteristics of OCT in patients of acquired immunodeficiency syndrome (AIDS) with cytomegalovirus retinitis (CMVR).MethodsThirty-nine eyes of 26 patients of AIDS with CMVR diagnosed in Department of ophthalmology of Beijing Ditan Hospital Capital Medical University from January 2015 to December 2017 were included in this study. All the patients were males, with the mean age of 33.12±9.87 years. All the patients underwent the OCT examination by Spectralis HRA+OCT. The locations of scanning were macular, optical papilla and posterior pole of retina with retinitis. Typical images were saved and analyzed.ResultsThe OCT pathological changes of CMVR included increase of retinal thickness and reflex of retina, indiscernible retinal layers, irregularity or absent external limiting membrane and/or ellipsoid zone, hyperreflective spots, vitreous cells. Among 39 eyes, there were 6 eyes with strong point-like reflection in the outer layer of retina around the lesion, 31 eyes (79.49%) with strong point-like reflection in the full layer of retina, 25 eyes (64.10%) with lesion involved macular area, 34 eyes (87.17%) with vitreous cells.ConclusionsOCT images of the eyes with AIDS with CMVR were characterized by lesions involving the whole retina. Absent ellipsoid zone or structural changes can be seen in the affected areas and peripheral areas of the lesion.
Objective To observe ocular manifestations of acquired immunodeficiency syndrome（AIDS）.Methods Fourtytwo AIDS patients（66 eyes）with ocular complaints received examinations of visual acuity, slit-lamp microscope, ophthalmoscope and fundus fluorescence angiography (FFA). The results were retrospectively analyzed. Results There are five types of ocular findings, including cytomegalovirus (CMV) retinitis (37 eyes, 56.0%), retinal microvasculopathy of human immunodeficiency virus (21 eyes, 32.0%), optic nerve diseases (three eyes, 4.5%), retinal neuroepithelial layer detachment (two eyes, 3.0%) and uveitis (three eyes, 4.5%).Conclusions The common ocular manifestations showed progressive necrotic retinitis, retinal hemorrhage and retinal vasculitis and attenuated，cotton-wool spots in AIDS patients.
ObjectiveTo observe the ultra-wide-angle fundus imaging characteristics of acquired immunodeficiency syndrome (AIDS) combined with cytomegalovirus retinitis (CMVR).MethodsThis 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.ResultsAmong 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).ConclusionThe 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.
ObjectiveTo analyze the sensitivity and specificity of polymerase chain reaction (PCR) tests in the detection of cytomegalovirus (CMV) in the diagnosis of patients with acquired immune deficiency syndrome (AIDS), using aqueous humor samples. Methods25 AIDS patients (including 21 men and 4 women) were studied. The age of the patients varied from 24 to 59 years, with an average of (39.2±9.3) years. The CD4+ T cell count was from 1 to 523 cells/μl, with a medium of 40 cells/μl. They were infected with human immunodeficiency virus(HIV)for a period from 15 days to 9 years with a median of 10 months. They were divided into three groups according to the fundus and treatment, including untreated cytomegalovirus retinitis (CMVR), treated CMVR and control group. There were 10 patients without anti-CMV treatment and 7 patients treated previously with foscarnet or ganciclovir whose eyes were diagnosed CMVR. Control group has 8 patients who had normal fundus or minor retinopathy excluded from CMVR. Approximately 100 μl of aqueous humor was obtained by anterior-chamber paracentesis and PCR was performed in all cases. ResultsThere were CMV DNA in 9 of 10 eyes with untreated CMVR (90.0% sensitivity). Of 7 specimens from eyes with treated CMVR, 3 were CMV PCR positive (42.9% sensitivity). All 8 samples of the control group were negative for CMV DNA, indicating the clinical specificity of our PCR was greater than 99.9% for CMVR. The anterior chamber paracentesis did not cause any complications in our patients except for a patient with subconjunctival hemorrhage. ConclusionsThe assay had an estimated sensitivity of 90.0% in detecting untreated CMVR and a sensitivity of 42.9% in detecting CMVR that had been treated. The specificity of this assay was greater than 99.9%.
Cytomegalovirus (CMV) retinitis (CMVR) is a common opportunistic infection of the eye after allogeneic hematopoietic stem cell transplantation in patients with hematological diseases. It often occurs within 3 months after the operation, with CMV activation and high blood CMV peaks. It often occurs on patients with long-term CMV viremia, human leukocyte antigen incompatible transplantation, unrelated donor transplantation, haploid transplantation, childhood hematopoietic stem cell transplantation, delayed lymphocyte engraftment, acute and chronic graft-versus-host disease after surgery. The visual prognosis of patients is related to the area of CMVR lesions on the retina, the number of quadrants involved, whether the macula is involved, and the CMV load of the vitreous body is involved, and it is not related to whether the Epstein-Barr virus infection is combined with blood and vitreous humor. The incidence of CMVR is increasing year by year. It is helpful that paying attention to systemic risk factors and epidemiology can provide more effective guidance for ophthalmologists during diagnosis and treatment, help patients improve the prognosis of vision, and reduce or even avoid the occurrence of blindness caused by CMVR.
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.
ObjectiveTo observe and preliminarily explore the relationship between the area of active fundus lesions and aqueous cytomegalovirus (CMV)-DNA in patients with acquired immunodeficiency syndrome (AIDS) with cytomegalovirus retinitis (CMVR).MethodsA retrospective study. From November 2019 to December 2020, the study population consisted of 22 AIDS patients (31 eyes) with active CMVR at the Beijing Ditan Hospital, Capital Medical University. All the patients were male. The age of the patients was 38.0±8.7 years. In total, 13 patients accepted highly active antiretroviral therapy (HAART). The median duration of treatment was 4 months. There were 9 cases that did not receive HAART. Ultra-wide-angle fundus imaging examination was performed using Optos P200T laser scanning ophthalmoscope. The software was used that comes with the device to measure the area of active lesions. Anterior chamber puncture was performed in all the affected eyes, 100 μl of aqueous humor was extracted, and the CMV-DNA load was quantitatively detected by polymerase chain reaction. At the same time, 19 cases of peripheral blood CD4+T lymphocytes and CMV-DNA load were tested; 17 cases of the human immunodeficiency virus (HIV)-RNA load were tested. The area of active lesions was used as the independent variable, and the CMV-DNA load of aqueous humor was used as the dependent variable to construct a linear regression function.ResultsAll eyes were active CMVR, with lesions ranging from 1 to 264 optic disc diameters, with a median of 43 optic disc diameters. Among 31 eyes, 30 eyes (96.8%, 30/31) had a median aqueous CMV-DNA load of 1.3×104 copies/ml, and one eye was negative for CMV-DNA in aqueous humor. In 19 patients who underwent peripheral blood CD4+ T lymphocyte detection, the median CD4+T lymphocytes were 18 cells/μl; 4 cases (21.1%, 4/19) were detected with CMV-DNA load. In the 17 patients who underwent HIV-RNA load testing, the median HIV-RNA load was 4.1×104 copies/ml. The results of correlation analysis showed that the amount of CMV-DNA in aqueous humor was significantly correlated with the size of active fundus lesions (r=0.601, P＜0.001), and was correlated with CD4+ T lymphocytes, CMV-DNA load in blood, and HIV-RNA load. There was no significant correlation between the amounts (r=0.125, 0.202, －0.096; P＞0.05). The regression equation was CMV-DNA load in aqueous humor = 3.38 + 0.01 × active lesion area.ConclusionThe amount of CMV-DNA in the aqueous humor is significantly correlated with the area of fundus active lesions, which can reflect the activity of fundus lesions.
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.
ObjectiveTo observe the safety and efficacy of regime that based on aqueous cytomegalovirus-DNA (CMV-DNA) load and IL-8 determination for therapeutic monitoring and local treatment cessation of cytomegalovirus retinitis (CMVR) patients after allogeneic hematopoietic stem cell transplantation (HSCT).MethodsA prospective case series study. A total of 14 CMVR patients (22 eyes) after allogeneic HSCT diagnosed in Ophthalmology Department of Peking University People's Hospital between January 2016 and December 2018 were involved in this study. All patients were CMV-DNA seronegative at baseline and were treated with intravitreous injection of ganciclovir (IVG, 3 mg in 0.05 ml) twice per week for 4 times in the induction stage and once a week in the maintenance stage. Aqueous humor sample was collected during the first time of IVG every week. CMV-DNA and the level of IL-8 were measured by real time quantitative PCR and ELISA, respectively. During follow-up, negative CMV-DNA (＜103/ml) or level of IL-8＜30 pg/ml in aqueous sample was set as local treatment cessation. Then patients were followed every 2 weeks for at least 6 months. BCVA, intraocular pressure and fundus examination were taken for each visit. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. BCVA and intraocular pressure at the baseline and the last follow-up were compared by the Student t matching test.ResultsOf the 14 CMVR patients (22 eyes) after allogeneic HSCT, 8 patients (16 eyes) were bilateral, 6 patients (6 eyes) were unilateral. At the baseline, the mean logMAR BCVA was 0.814±0.563, the intraocular pressure was 17.2±7.8 mmHg (1 mmHg=0.133 kPa), the mean aqueous CMV-DNA load was (3.43±4.96)×105/ml, the mean level of IL-8 was 518±541 pg/ml. At cessation of local treatment, the median number of intravitreal injections was 5 times. Nine eyes showed negative CMV-DNA in aqueous humor, of which, 7 eyes showed negative IL-8 in aqueous. CMV-DNA could still be detected in 13 eyes, while IL-8 was negative. Only one eye’s retinal lesion was completely quiet. Six months after local treatment cessation, the mean logMAR BCVA was 0.812±0.691, the intraocular pressure was 14.8±5.4 mmHg; which was not significantly different from baseline (t=-0.107, 1.517; P=0.916, 0.137). Recurrence of CMVR happened in only 1 eye because of systemic EB virus infection. Retinal lesions progressively improved and became completely quiet in all the remaining 20 eyes. In 22 eyes, iatrogenic vitreous hemorrhage occurred due to low platelet count during treatment (＜30×109/ml) in 4 eyes. When the treatment was terminated for 6 months, the fundus of hematoma absorption was clearly visible. At the time of CMVR diagnosis, there were 2 eyes (9%) with posterior subcapsular opacity, which may be caused by systemic glucocorticoid therapy after allogeneic HSCT.ConclusionAqueous CMV-DNA load and level of IL-8 could be used as quantitative variables for monitoring the therapeutic effect and determining time for local treatment cessation for CMVR after HSCT safely and efficiently.