The etiology of intraocular inflammatory disease and its diagnosis is complicated. Currently available and newly emerging systemic and ocular examinations are of important to determine etiology of intraocular inflammatory disorders. But there also exists multiple misunderstanding, and the strategy of their application is not well defined, or even exaggerated. Unprincipled or randomly selection of auxiliary examination would not help for etiology determination, but bring unnecessary pain and economic burden to patients. Establishment of diagnosis thinking of intraocular inflammatory disease is helpful to standardize the diagnosis process of the disease, improve the diagnostic efficiency, and relief patients from the pain and financial burden that caused by too many useless examinations.
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.
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.
Retinal vein occlusion (RVO) is one of the most important retinal vascular diseases in China that leads to severe loss of vision. In recent years, the emergence of various emerging imaging technologies and new drugs has not only deepened our understanding of the natural course of this disease, but also significantly changed the traditional treatment mode of retinal laser photocoagulation as the gold standard, thereby significantly improved the visual prognosis. However, currently in various regions and levels of hospitals in China, the diagnosis and treatment of RVO still rely mainly on their own experience. The awareness and knowledge of RVO among ophthalmologists in various regions still need to be improved. A standardized clinical diagnosis and treatment pathway is needed in order to meet the needs of most RVO patients. Led by the Fundus Disease Group of the Ophthalmology Branch of the Chinese Medical Association and the Fundus Disease Professional Committee of the Ophthalmology Branch of the Chinese Medical Association, based on the existing evidence-based evidence at home and abroad, and following the principles of consensus formulation, Expert consensus on clinical diagnosis and treatment path of retinal vein occlusion in China has been compiled. The consensus systematically and comprehensively elaborated a standardized diagnosis and treatment pathway for RVO. Interpreting the key points in this consensus is helpful to highlight the core ideas, and improve the utilization of this consensus by ophthalmologists from all levels of hospitals.
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 observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet. MethodsA retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age (Z=－0.447), gender composition (Z=－0.485), logMAR BCVA (t=－1.591), intraocular pressure (t=－0.167) and CMT (t=－1.290) between two groups (P＞0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. ResultsAt baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA (t=4.129) and CMT (t=－0.713) were significantly improved, with statistical significance (P＜0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times (t=－1.275), logMAR BCVA (t=－0.492), intraocular pressure (t=0.351) and CMT (t=－1.783) between the two groups (P＞0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. ConclusionShort-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.