ObjectiveTo evaluate the safety and efficacy of the intravitreal methotrexate treatment in patients with primary vitreoretinal lymphoma (PVRL). MethodsRetrospective non-comparative interventional case series. Fourteen patients (26 eyes) with biopsy-proven PVRL were included in the study. All patients received examination of Snellen chart visual acuity, fundus color photography and optical coherence tomography (OCT). Among the 24 eyes with recordable visual acuity, 17 eyes has initial visual acuity≥0.1 (0.45±0.20) and 7 eyes with initial visual acuity ranged from light perception to hand movement. The vitreous opacities and (or) subretinal yellowish-white lesions and retinal pigment epitheliumuplift were observed in all eyes. All eyes were treated with intravitreal methotrexate (4000 μg/ml, 0.1 ml) injections according to a induction-consolidation-maintenance regimen. For 26 treated eyes, each received an average of (11.5±6.3) injections. Twenty eyes had finished theintraocular chemotherapy, while 6 eyes had not. Eight of 20 eyes were clinically confirmed free of tumor cells by diagnostic vitrectomy, 12 eyes were still with tumor cell involvement.The follow-up was ranged from 2 to 48 months, the mean time was 18 months. The examination of BCVA, fundus color photography and OCT were performed. No tumor cell was defined as clinical remission. Visual acuity was scored as improved or declined obviously (improved or declined 2 lines) or mild improved or declined (changed within 2 lines). ResultsTwenty eyes achieved clinical remission after (3.5±3.6) injections, 12 eyes of 20 eyes with tumor cell involvement before chemotherapy achieved clinical remission after (5.8±3.0) injections. The mean visual acuity of seventeen eyes with initial visual acuity 0.1 in induction phase and at the end of treatment were 0.36±0.23 and 0.56±0.20, respectively. Compared with before treatment, the visual acuity was mild declined in induction phase (t=1.541, P>0.05), but mild improved at the end of treatment (t=2.639, P<0.05). The visual acuity at the end of treatment in 7 eyes with initial visual acuity<0.1 was ranged from no light perception to 0.1. Of 14 patients, 2 patients have been fatal because of brain lesions progression at 42 and 48 months after diagnosis of primary central nervous system lymphoma. No ocular recurrence was noted during the follow-up in 20 eyes who finished intraocular chemotherapy. ConclusionsPVRL patients can achieve clinical remission after (3.5±3.6) injections by intravitreal chemotherapy of methotrexate, and the visual acuity improved mildly. No ocular recurrence was found during follow-up.
ObjectiveTo compare and analyze the application of anti-vascular endothelial growth factor (VEGF) drugs for intravitreal injection in the real world before and after the establishment of one-stop intravitreal injection center, as well as the advantages and disadvantages of different management modes. MethodsA retrospective clinical study. A total of 4 015 patients (4 659 eyes) who received anti-VEGF drugs for ocular fundus diseases at the Tianjin Medical University Eye Hospital from July, 2018 to June, 2022 were included in the study. There were 2 146 males and 1 869 females. The ocular fundus diseases in this study were as follows: 1 090 eyes of 968 patients with wet age-related macular degeneration (wAMD); 855 eyes of 654 patients with diabetic macular edema (DME); 1 158 eyes of 980 patients with diabetic retinopathy (DR); 930 eyes of 916 patients with macular edema secondary to retinal vein occlusion (RVO-ME). A total of 294 eyes of 275 patients with choroidal neovascularization secondary to pathological myopia (PM-CNV); 332 eyes of 222 patients with other fundus diseases. A total of 13 796 anti-VEGF needles were injected. A total of 1 252 patients (1 403 eyes) from July 2018 to June 2020 were regarded as the control group. From July 2020 to June 2022, 2 763 patients (3 256 eyes) who received anti-VEGF treatment in the intravitreal injection center were regarded as the observation group. The total number of intravitreal injection needles, the distribution of anti-VEGF therapy in each disease according to disease classification, the proportion of patients who chose the 3+ on-demand treatment (PRN) regimen and the distribution of clinical application of different anti-VEGF drugs were compared between the control group and the observation group. The waiting time and medical experience of patients were investigated by questionnaire. χ2 test was used to compare the count data between the two groups, and t test was used to compare the measurement data. ResultsAmong the 13 796 anti-VEGF injections in 4 659 eyes, the total number of anti-VEGF drugs used in the control and observation groups were 4 762 and 9 034, respectively, with an average of (3.39±3.78) and (2.78±2.27) injections per eye (t=6.900, P＜0.001), respectively. In the control and observation groups, a total of 1 728 and 2 705 injections of anti-VEGF drugs were used for wAMD with an average of (5.14±4.56) and (3.59±2.45) injections per eye, respectively; a total of 982 and 2 038 injections of anti-VEGF drugs were used for DME with an average of (4.36±4.91) and (3.24±2.77) needles per eye, respectively. Additionally, a total of 942 and 2 179 injections of anti-VEGF drugs were injected for RVO-ME with an average of (3.98±3.71) and (3.14±2.15) injections per eye, respectively; a total of 291 and 615 injections of anti-VEGF drugs were injected for PM-CNV with an average of (3.31±2.63) and (2.99±1.69) injections per eye, respectively. A total of 683 and 1 029 injections of anti-VEGF drugs were injected for DR with an average of (1.60±1.26) and (1.41±1.05) injections per eye, respectively. The clinical application and implementation of "3+PRN" treatment were as follows: 223 (66.4%, 223/336) and 431 eyes (57.2%, 431/754) in the wAMD (χ2=8.210, P=0.004), 75 (33.3%, 75/225) and 236 (37.5%, 236/630) eyes in the DME (χ2=1.220, P＞0.05), and 97 (40.9%, 97/237) and 355 eyes (51.2%, 355/693) in the RVO-ME (χ2=7.498, P=0.006), 39 (44.3%, 39/88) and 111 eyes (53.9%, 111/206) in the PM-CNV ( χ2=2.258, P＞0.05), respectively. In addition, the results of the questionnaire survey showed that there were significant differences between the control and observation groups regarding the time of appointment waiting for surgery (t=1.340), time from admission to entering the operating room on the day of injection (t=2.780), time from completing preoperative treatment preparation to waiting for entering the operating room (t=8.390), and time from admission to discharge (t=6.060) (P＜0.05). ConclusionsThe establishment of a one-stop intravitreal injection mode greatly improved work efficiency and increased the number of injections. At the same time, the compliance, waiting time, and overall medical experience of patients significantly improved under centralized management.
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.
Gene therapy is designed to introduce genetic material into the cells of a patient via virus to enhance, inhibit, edit or add a genetic sequence, results in a therapeutic or prophylactic effect. Gene therapy has brought positive influence and great potential for the treatment of retinal diseases including genetic retinal diseases and acquired retinal diseases. In addition to the constant optimization of gene vectors, the exploration of different drug delivery techniques has brought different therapeutic effects for gene therapy of retinal diseases. The main delivery methods include subretinal injection, intravitreal injection, suprachoroidal injection. Considering the transfection efficiency and safety of delivery methods, emerging sub-inner limiting membrane injection and noninvasive gene delivery are under investigation. The selection of gene delivery method is very important for the safety and effectiveness of gene therapy for retinal diseases. It is not only related to the development of equipment and technology, but also related to the modification of adeno-associated virus, the selection of promoter and the specific retinal cells that the target gene wants to be transfected. Therefore, the most appropriate method of gene delivery should be selected according to the final gene therapy agent and the specific transfected cells after taking all these factors into consideration.
ObjectiveTo investigate the clinical effects and influence factors of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs in the treatment of idiopathic choroidal neovascularization (ICNV). MethodsThis retrospective study involved 27 patients (27 eyes) with ICNV from July 2012 to July 2015. Patients received intravitreal bevacizumab (1.25 mg), ranibizumab (0.05 mg), additional injection was provided if it was needed. The average follow-up time was 168 weeks. The recovery of best corrected visual acuity (BCVA) and central foveal retinal thickness (CRT) of the affected eye was observed. Follow up once a month after the initial treatment until the lesion was completely absorbed or scarred (the first follow-up period). Follow up every 12 weeks was performed to observe the recurrence of the lesions (the second stage of long-term follow-up). One month after the last injection of the first follow-up period, according to the regression of choroidal neovascularization (CNV), the affected eyes were divided into a significant improvement group (significant improvement group) and an insignificant improvement group (non-significant improvement group)), to analyze the effects of age, course of disease, type of drugs, number of injections, baseline BCVA and CRT on the regression of CNV lesions. According to the results of long-term follow-up, the eyes were divided into recurrence group and non-recurrence group, and the factors affecting the recurrence of CNV lesions were analyzed. Measurement data between groups was compared by using independent sample t test or non-parametric test; count data was compared by using χ2 test. Logistic regression analysis was used to analyze the factors affecting the regression and recurrence of the lesion. ResultsAt baseline and 1 month after the last injection in the first stage, the average BCVA of the eyes were 55.70±15.21 and 73.59±12.08 letters; CRT was 338.3±89.32 and 264.5±47.47 μm, respectively. The BCVA and CRT of the affected eyes were compared at the two time points, and the differences were statistically significant (Z= －3.886, －4.061; P＜0.001). The BCVA of the eyes in the significant improvement group and the insignificant improvement group were 65.38±17.27 and 51.63±12.61 letters, respectively; the difference between the two groups of BCVA was statistically significant (t=－2.316, P=0.029). The results of long-term follow-up showed that of the 27 eyes, 6 eyes had recurrence; the average recurrence time was 90.83±49.02 weeks. After another intravitreal injection of anti-VEGF drugs, the CNV lesions was resolved. The average injection times of the relapsed group and the non-relapsed group were 3.67±0.816 and 2.24±0.768, respectively. The average injection times of the relapsed group was significantly higher than that of the non-relapsed group, and the difference was statistically significant (Z=－3.253, P＜0.001). There was no statistically significant difference between the two groups of eyes at baseline and CRT at the last follow-up (Z=－1.342,－1.313; P=0.195, 0.195). ConclusionIntravitreal injection of anti-VEGF drugs can effectively increase the regression rate of BCVA and CNV lesions in ICNV eyes; high baseline visual acuity indicates better CNV lesion regression after treatment. Relapsed patients can be effectively improved after re-treatment with anti-VEGF drugs, and CNV recurrence has no significant effect on the final prognosis.
Primary vitreoretinal lymphoma (PVRL) is a rare type of non-Hodgkin's lymphoma with poor prognosis and the optimal treatment has yet to be determined. Its treatment has evolved from enucleation to ocular radiotherapy, systemic chemotherapy and intravitreal chemotherapy. Radiotherapy can effectively eradicate tumor cells but ocular recurrences are common. Systemic chemotherapy has become the mainstream option but there are problems with only-partial response of PVRL and high rate of recurrence. Intravitreal chemotherapy, primarily used as adjunctive to systemic chemotherapy, has achieved high remission rate and low rate of recurrence as well as with limited ocular complications. The tumor cells were cleared and the visual function preserved. However, issues about the drug applied, treatment protocols and goals of intravitreal chemotherapy, whether for visual preservation or survival improvement, are worthy for further study.
ObjectiveTo observe the ocular clinical features and efficacy of young infants with incontinentia pigmenti (IP). MethodsA retrospective study. Clinical data of 18 young infants with IP aged 0-3 months in the Department of Ophthalmology of Henan Children's Hospital from October 2017 to February 2019 were collected in this study. All patients were underwent fundus examination under topical anesthesia or general anesthesia. Among them, 9 cases were underwent genetic testing. Patients were determined whether to treated with retinal laser photocoagulation (LIO) or intravitreal conbercept (IVC, 0.25 mg/0.025 ml) according to the condition of eyes. The followed-up time ranged from 4months to 43 months. The ocular clinical features and treatment were observed. ResultsThere were 1 male and 17 females of the 18 patients. The age of first visit were 1.2±1.0 months (2 d-3 months). All cases had typical skin lesions, 4 cases had neurological symptoms, 10 cases had tooth abnormalities, and 4 cases had cicatricial alopecia. Among the 9 cases that were underwent genetic testing, 5 cases were deleted in exons 4-10 of the IKBKG gene and 1case were a heterozygous mutation c.1124delT in exon 9 of the IKBKG gene. Among the 36 eyes, 21 eyes of 13 cases with incontinentia pigmenti-associated ocular diseases were all retinopathy (58.3%,21/36). Retinopathy of 9 cases were asymmetrical (69.2%,9/13). Among the 21 eyes, 3 eyes were simple retinal pigment abnormalities (14.3%,3/21) and 18 cases had retinal vascular lesion (85.7%, 18/21). Among the 36 eyes, 8 eyes were treated; 4 eyes were underwent LIO; 3 eyes were treated with IVC; 1 eye was treated with LIO combined with IVC. They were all improved significantly after the operation without serious complications. 1 eye with retinal detachment did not undergo surgical treatment due to guardian reasons. Perceptual exotropia and eyeball atrophy was found during the follow-up. ConclusionsThe onset of IP-related ocular anomalies is early. The early anomalies were mainly retinal vascular abnormalities. Treatment in early time is effective.
ObjectiveTo observe the efficacy of parsplana vitrectomy (PPV) combined with 0.7 mg dexamethasone sustained-release Ozurdex intravitreal implantation in the treatment of children with ocular toxocariasis (OT). MethodsA retrospective clinical study. Fifty-three pediatric patients (53 eyes) diagnosed with OT and underwent PPV in Beijing Tongren Eye Center of Beijing Tongren hospital from March 2015 to December 2021 were included. There were 30 males and 23 females, with an average age of 7.07±3.45 (4-14) years; all were unilateral. Color Doppler imaging, fundus color photography, optical coherence tomography examinations were performed for patients who can cooperated with the examiners. Forty-three eyes were examined by best corrected visual acuity (BCVA); 47 eyes were examined by intraocular pressure; 29 eyes were examined by ultrasound biomicroscopy. According to the location of granuloma, OT was divided into posterior pole granulomatous type (posterior type), peripheral granulomatous type (peripheral type), and chronic endophthalmitis type. According to whether Ozurdex was implanted into the vitreous cavity after PPV, the children were divided into the oral glucocorticoid group after PPV (group A) and the PPV combined with vitreous cavity implantation of Ozurdex group (group B), 37 cases with 37 eyes and 16 cases with 16 eyes, respectively. There was no significant difference in age (t=0.432), sex composition ratio (χ2=0.117), BCVA (χ2=0.239), and clinical type (χ2=0.312) between the two groups (P＞0.05). The follow-up time after surgery was ≥5 months. The intraocular pressure at 1 week and 1, 3, and 6 months after surgery, the changes of BCVA and the occurrence of complications such as concurrent cataract and epimacular membrane were observed at the last follow-up, and the incidence of obesity in the children during the follow-up period was recorded. The measurement data between groups was compared by independent sample t test; the enumeration data was compared by χ2 test. ResultsOne month after the operation, the intraocular pressure of group A and group B were 15.17±6.21 and 25.28±10.38 mm Hg (1 mm Hg=0.133 kPa) respectively; the intraocular pressure of group B was significantly higher than that of group A, the difference was statistically significant (t=0.141, P=0.043). At the last follow-up, there was no significant difference in the percentage of visual acuity improvement between the two groups (χ2=0.315, P=0.053); there was no significant difference in the incidence of concurrent cataract and epimacular membrane (χ2=0.621, P＞0.05). Among the 37 cases in group A, 32 cases (86.5%, 32/37) developed obesity symptoms during the follow-up period. ConclusionPPV combined with intravitreal implantation of Ozurdex and oral glucocorticoid after PPV can effectively improve the visual acuity of the affected eye; the incidence of complications is similar, however, the incidence of obesity after oral glucocorticoid is higher.
Nowadays, one of the most challenging aspects of retinoblastoma (RB) therapy is how to control the resistant or recurrent viable vitreous seeds, for which intravenous chemotherapy appears to be ineffective. Recently, intravitreal chemotherapy offers another option to control advanced stage and vitreous seeds of RB, and may be a promising new approach to RB therapy. However, intravitreal injection for RB patients raises considerable controversy due to concerns of possible extraocular extension along the injection route, and should not replace the primary standard of care for bilateral RB or group E eyes of RB. Close follow-up and further studies are needed to determine appropriate indications, to determine the effective drugs and concentrations, to optimize RB therapy protocols and to investigate the relationship between long-term efficacy and toxicities.
Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.