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.
Objective To observe the clinical characteristics and treatment of cytomegalovirus retinitis (CMVR) in leukemia patients. Methods This is a retrospective analysis. Seven leukemia patients (13 eyes) with CMVR were studied. All patients underwent examinations of visual acuity, slit lamp microscope, ophthalmoscope, color fundus photography, peripheral blood CD4+T cell count and serum/aqueous CMV-DNA test. All patients were treated with ganciclovir or zoledronic acid combined with intravitreal injection of ganciclovir. The follow-up period was 3-14 months. Results Six patients were treated with hematopoietic stem cell transplantation and 1 patient was with chronic leukemia. All patients were CMV-DNA positive for serum, and 18.5% (2/7) for aqueous humor. CMVR in leukemia patients showed mild anterior segment inflammation, ocular fundus with irregular yellowish-white retinal necrosis and radial hemorrhage (7 eyes). Some (2 eyes) also shoed gray and white granular retinal infiltrates. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of high concentration ganciclovir was an effective treatment, while systemic corticosteroids were effective in reducing vitreous opacity. Conclusions CMVR is characterized by progressive necrotic retinitis with hemorrhage and vasculitis. Intravenous ganciclovir/zoledronic acid combined with intravitreal injection of ganciclovir is effective in the treatment of CMVR with leukemia.
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 investigate the clinical manifestations of acquired immunodeficiency syndrome(AIDS) patients with initial-stage cytomegalovirus (CMV) retinitis (CMVR).MethodsRetrospective 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.ResultsThere 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).ConclusionThe 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.
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 aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment. MethodsA retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration. ResultsAt the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [R2=0.385, P＜0.000 1, B=－0.237 log10 copies/(ml · time)], and the duration of treatment [R2=0.394, P <0.000 1, B=－0.301 log10 copies/(ml · week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity (t=－1.223), intraocular pressure (t=1.538), aqueous humor CMV-DNA load (t=－0.109), retinitis lesion area (Z=－0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved (Z=－0.024) and whether the macula was involved (Z=－1.826), combined with anterior segment inflammation (Z =－0.499), combined with high intraocular pressure (Z=－1.342), terminal visual acuity (t =－0.845), intraocular pressure (t=－0.068), total IVG times (Z=0.907), age (Z=－0.832), gender composition (Z=－1.074), etc. The difference was not statistically significant (P＞0.05). ConclusionThe CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.
Objective To evaluate the clinical features, diagnosis, and outcome of the treatment of cytomegalovirus (CMV) retinitis, and the relationship between CMV retinitis and acquired immunodeficiency syndrome (AIDS). Methods A total of 95 eyes of 56 patients with cytomegalovirus retinitis and AIDS were studied. The fundus feature, visual acuity and CD4+ T-lymphocyte counts were analyzed and the follow-up periods ranged from 2 weeks to 18 months. Results Before the definitive diagnosis of CMV retinitis, the courses of AIDS were 4 to 26 months in all patients. In the initial examination, the granular form of CMV retinal lesion was noted in 55 eyes (57%) in which retinal lesion of 46 eyes was peripheral. The fulminant form of CMV retinitis of 25 eyes (26%) was found in the posterior pole and consisted of densely opaque retinal lesions with blotchy hemorrhage and vasculitis. The overlap between these two presentations was noted in 15 eyes. Papillitis was observed in 7 eyes of CMV retinitis in this series of patients. The visual acuity ranged from finger counting to 0.5. The patients with extensive CMV retinitis or CMV retinitis in the posterior pole got poorer vision. The CD4+ T-lymphocyte counts of 30 patients was 0-30 (mean, 15±9/μl), and the survival time ranged from 2 weeks to 18 months (mean, 6.4±3.3 months). The vision was improved and CD4+ T-lymphocyte counts was significantly higher in the group treated with ganciclovir, and progression of CMV retinitis occured and the vision decreased in the non-treated group. Conclusion CMV retinitis is the most common intraocular complication in patients with AIDS. Diagnosis of CMV retinitis is based on the characteristic of necrotizing retinitis which was typically associated with retinal hemorrhage and vasculitis. Ganciclovir is effective for the treatment of CMV retinitis. (Chin J Ocul Fundus Dis, 2002, 18: 89-91)
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.
ObjectiveTo observe the clinical features of cytomegalovirus (CMV) retinitis (CMVR)-related uveitis after hematopoietic stem cell transplantation (HSCT).MethodsA retrospective clinical study. From October 2015 to May 2020, 14 cases of 21 eyes of CMVR patients with CMVR after HSCT confirmed by the ophthalmological examination of The First Affiliated Hospital of Soochow University were included in the study. Among them, there were 5 males with 8 eyes and 9 females with 13 eyes. The average age was 35.12±12.24 years old. All the affected eyes were examined by slit lamp microscope combined with front lens and fundus color photography. At the same time, fluorescein fundus angiography (FFA) was performed to examine 10 eyes of 5 cases; 3 cases of 3 eyes were examined for inflammatory cytokines in aqueous humor. All eyes received intravitreal injection of ganciclovir; patients with a history of systemic CMV infection received intravenous infusion of ganciclovir/foscarnet. The retinal lesions in the eye were completely resolved or the aqueous CMV-DNA was negative as a cure for CMVR. The uveitis symptoms, signs, FFA manifestations and the test results of inflammatory factors in aqueous humor before and after the CMVR cure was observed. The follow-up time after CMVR was cured was 3-42 months, and the average follow-up time was 14.28±13.12 months.ResultsAll eyes with CMVR were diagnosed with retrocorneal dust and/or stellate keratic precipitates (KP), anterior chamber flare and cells, and varying degrees of vitreous flocculent opacity; the retina was typical of a mixture of hemorrhage and yellow-white necrosis like "scrambled eggs with tomatoes". After CMVR was cured, there were 16 eyes (71.4%, 10/14) in 10 cases with KP, anterior chamber flare, cell and vitreous opacity. FFA examination revealed that the majority of retinal leakage during the active period of CMVR was necrotic foci and surrounding tissues; after CMVR was cured, the majority of retinal leakage was the retina and blood vessels in the non-necrotic area. The test results of inflammatory factors in aqueous humor showed that interleukin (IL)-6, IL-8, and vascular endothelial cell adhesion molecules were significantly increased in the active phase of CMVR; after 3 months of CMVR cured, inflammatory factors did not increase significantly.ConclusionCMVR-associated uveitis after HSCT show as chronic panuveitis, with no obvious eye congestion, KP, anterior chamber flare, cell and vitreous opacity, and retinal vessel leakage which could exist for a long time (＞3 months).
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.