ObjectiveTo observe the clinical efficacy of dexamethasone intravitreal implant (DEX) in the treatment of active non-infectious uveitis macular edema (NIU-ME).MethodsA retrospective observational study. From February 2018 to February 2019, 23 patients (26 eyes) were included in the study who were diagnosed with NIU-ME at the Department of Ophthalmology, Central Theater Command General Hospital and received intravitreal DEX treatment. Among 23 patients, there were 8 males (8 eyes) and 15 females (18 eyes); the average age was 46.9 years; the average course of disease was 9.2±2.4 months. All the affected eyes underwent BCVA and intraocular pressure examination; at the same time, OCT was used to measure the central retinal thickness (CMT) of the macula. Snellen visual acuity chart was used for visual inspection. The average BCVA of the affected eye was 0.281±0.191, the average intraocular pressure was 16.2±0.8 mmHg (1 mmHg=0.133 kPa), and the average CMT was 395.4±63.7 μm. Among the 23 patients, 8 patients had middle uveitis and 15 patients had posterior uveitis. Seven patients had received intravenous infusion of methylprednisolone, 5 patients had been treated with methylprednisolone combined with immunosuppressive agents, and 11 patients had not received any treatment. All the affected eyes were treated with DEX intravitreal injection. Patients received repeated visual acuity, intraocular pressure and OCT examination with follow-up after injection. During the follow-up period, patients with recurrence of edema or poor efficacy, systemic methylprednisolone and intravitreal reinjection of DEX, triamcinolone acetonide or methotrexate should be considered based on the patient's own conditions. We observed the changes of BCVA, intraocular pressure and CMT before and after injection in the affected eyes, and analyzed the variance of a single repeated measurement factor. At the same time, we observed the occurrence of ocular adverse reactions and systemic complications.ResultsAfter treatment 1.2±0.4, 3.3±0.3, 6.7±1.1, 9.2±1.1, 12.2±0.6 months, the BCVA of the affected eyes were 0.488±0.296, 0.484±0.266, 0.414± 0.247, 0.411±0.244 and 0.383±0.232; CMT was 280.2±42.7, 271.0±41.4, 292.5±42.9, 276.2±40.5, 268.4±26.6 μm, respectively. Compared with before treatment, the BCVA and CMT of the all eyes increased after treatment, and the difference was statistically significant (F=30.99, 5 196.92; P＜0.000). Among 23 eyes completed a 12-month follow-up, 13 eyes (56.5%) received 2 injections, 3 eyes (13.0%) received 3 injections, and other 7 eyes (30.4%) received only 1 injection. After treatment 1.2±0.4 months, 5 patients (6 eyes) with intraocular pressure＞25 mmHg gradually returned to normal after treatment with two eye drops for lowering intraocular pressure; 1 patient (2 eyes) with intraocular pressure＞40 mmHg, the intraocular pressure gradually returned to normal after 3 kinds of eye drops for lowering intraocular pressure.ConclusionIntravitreal injection of DEX in the treatment of NIU-ME can improve the visual acuity of the affected eye and reduce CMT.
Objective To evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO). Methods This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n=129) or sham procedure (n=130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography. Results Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (P＜0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 34.9%, sham: 11.5%; mean BCVA change from baseline was DEX: 10.6±10.4 letters, sham: 1.7±12.3 letters; and mean CRT change from baseline was DEX: ?407±212 μm, sham: ?62±224 μm (all P＜0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was in-creased intraocular pressure (IOP). Increase sin IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery. Conclusions DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3 - 4 months after a single implant.
Intravitreal drug injection is a treatment for common chronic fundus diseases such as age-related macular degeneration and diabetic retinopathy. The “14th Five-Year” National Eye Health Plan (2021-2025) recommends focusing on fundus diseases and improve the management mode of patients with chronic eye diseases. Therefore, it is imperative to explore how to further optimize the service process of intravitreal injection under the premise of guaranteeing patients' medical safety, to promote medical service efficiency and standardized management level and improve the medical experience of patients. Based on the quality control standard of vitreous cavity injection for retinopathy in China, Chinese fundus disease and related field experts developed the present expert consensus on the establishment of a one-stop intravitreal injection model and the management of its organization after a serious, comprehensive, and complete discussion, focusing on a standardized operation process, quality control, and safety management, providing more references for establishing a suitable intravitreal injection management model for ophthalmology and promoting the development of diagnostic and treatment models for fundus disease in China.
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.
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.
ObjectiveTo compare the efficacy of pars plana vitrectomy (PPV) combined with subretinal or intravitreal injection of Conbercept for the treatment of refractory diabetic macular edema (DME). MethodsA retrospective case control study. From June 2022 to March 2024, 32 eyes of 32 patients with refractory DME diagnosed at The Affiliated Eye Hospital of Nanchang University were included in the study. There were 17 male cases with 17 eyes and 15 female cases with 15 eyes. Age was (57.44±8.99) years old; The duration of diabetes was (12.72±6.11) years. All patients had received regular treatment with anti-vascular endothelial growth factor (VEGF) drugs or corticosteroid drugs for at least 5 times, and had undergone focal retinal laser photocoagulation or panretinal laser photocoagulation, the central macular thickness (CMT) persisted or decreased by less than 50 μm. All affected eyes underwent best-corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT), microperimetry, and laboratory glycated hemoglobin (HbA1c) testing. BCVA was measured using a standard logarithmic visual acuity chart, and converted to the logarithm of the minimum angle of resolution (logMAR) for statistical analysis. CMT was measured using an OCT device. Microperimetry was performed using an MP-3 microperimeter, recording the mean sensitivity (MS) of the retina within a 12° range of the fovea. The affected eyes were treated with 23G PPV combined with internal limiting membrane peeling and either macular subretinal or intravitreal injection of Conbercept, and were divided into subretinal injection group and the intravitreal injection group, each consisting of 16 cases and 16 eyes. The same equipment and methods as before surgery were used for related examinations at 1, 3, and 6 months post-surgery. Changes in BCVA, CMT, and MS were observed and compared, as well as the number of additional anti-VEGF treatments required within 6 months after surgery. Intergroup comparisons were made using independent samples t tests, and repeated measures data were analyzed using repeated measures analysis of variance. ResultsThe age (t=－0.271), gender composition (χ2=0.001), duration of diabetes (Z=－0.868), HbA1c (t=－0.789), intraocular pressure (t=1.689), logMAR BCVA (t=1.393), CMT (t=－0.613), MS (Z=－0.132), and the number of anti-VEGF injections (t=－0.752) between the subretinal injection group and the intravitreal injection group showed no statistically significant differences (P＞0.05). The within-subject effects comparison of BCVA, CMT, and MS at 1, 3, and 6 months post-surgery compared to pre-surgery for all affected eyes showed statistically significant differences (F=8.060, 125.722, 39.054; P＜0.05). The overall comparison of logMAR BCVA between the subretinal and intravitreal injection groups post-surgery showed no statistically significant difference (F=0.662, P=0.422), however, comparisons of CMT (F=4.540) and MS (F=6.066) showed statistically significant differences (P＜0.05). At 1, 3, and 6 months post-surgery, comparisons of logMAR BCVA between the two groups showed no statistically significant differences (t=－0.123, 0.239, 1.087; P＞0.05), comparisons of CMT showed statistically significant differences (t=－3.474, －4.832, －2.482; P＜0.05), comparisons of MS showed statistically significant differences at 1 and 3 months (t=－2.940, －2.545; P＜0.05), but not at 6 months (t=－1.527, P＞0.05). At 6 months post-surgery, the number of additional intravitreal anti-VEGF injections required in the subretinal and intravitreal injection groups showed a statistically significant difference (Z=－2.033, P=0.042). During the follow-up period and at the final follow-up, no complications such as injection site bleeding, retinal detachment, vitreous hemorrhage, macular hole, or retinal pigment epithelial tear or atrophy occurred in all affected eyes. ConclusionCompared with intravitreal injection, subretinal injection of Conbercept for the treatment of refractory DME has more advantages in reducing macular edema and improving visual function in the macular area, and also reduces the number of postoperative anti-VEGF drug treatments.
ObjectiveTo observe the short-term efficacy and safety of a new strategy of dexamethasone intravitreal implant (DEX) combined with ranibizumab in the treatment of retinal vein occlusion (RVO) secondary to macular edema (ME) (RVO-ME). MethodsA prospective clinical interventional study. From May 2020 to September 2021, 78 RVO-ME patients with 78 eyes diagnosed in the eye examination of Department of Ophthalmology of The First Affiliated Hospital of Anhui University of Science&Technology were included in the study. Among them, there were 35 males and 43 females, all with monocular disease. Branch retinal vein occlusion (BRVO) was found in 40 patients with 40 eyes; central retinal vein occlusion (CRVO) was found in 38 patients with 38 eyes. According to the treatment strategies, patients were randomly divided into DEX and ranibizumab combination therapy group (initial combination therapy group), DEX monotherapy group and ranibizumab monotherapy group, with 29 eyes, 26 eyes and 23 eyes respectively. Different types of RVO were divided into different treatment groups of BRVO and CRVO. Best corrected visual acuity (BCVA) and frequency domain optical coherence tomography were performed. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. There were no significant differences in logMAR BCVA (χ2=2.376) and central retinal thickness (CRT) (F=0.052) among the three groups (P＞0.05). After treatment, the patients were followed up every month for 6 months. The changes of BCVA, CRT and the incidence of adverse reactions were observed during follow-up. One-way ANOVA and Kruskal-Wallis H test were used to compare the differences. ResultsDuring the follow-up period, compared with the baseline, the BCVA of the eyes in the initial combination treatment group, DEX treatment group and ranibizumab treatment group were significantly improved (Z=110.970, 90.359, 207.303), and CRT was significantly decreased (F=107.172, 88.418, 61.040), the difference was statistically significant (P＜0.01). At 1, 2, 3, 4, 5, and 6 months after treatment, there were significant differences in the mean changes in BCVA between the initial combined treatment group, DEX treatment group, and ranibizumab treatment group (χ2=34.522, 29.570, 14.199, 7.000, 6.434, 6.880; P＜0.05); 1, 2, 3, and 6 months after treatment, the differences were statistically significant (F=4.313, 7.520, 3.699, 3.152; P＜0.05). The time required to improve BCVA by 0.1 logMAR units in the initial combination treatment group, DEX treatment group, and ranibizumab treatment group was 5.73 (3.21, 8.48), 9.97 (6.29, 18.78), and 20.00 (9.41, 37.89) d, respectively; The time required for CRT to drop to 300 μm was 24.31 (21.32, 26.15), 29.42 (25.65, 31.37), and 29.17 (25.28, 36.94) d, respectively. The BCVA improvement of 0.1 logMAR unit and the time required for CRT to decrease to 300 μm in the eyes of initial combined treatment group were shorter than those in the eyes of DEX treatment group and the ranibizumab treatment group, and the differences were statistically significant (Z=－3.533, －4.445, －3.670, －4.030; P＜0.01). Different BRVO treatment groups: 1, 2, 3, 5, and 6 months after treatment, the mean BCVA changes were significantly different (χ2=24.989, 21.652, 11.627, 7.054, 9.698; P＜0.05); CRVO was different treatment group: 1 and 2 months after treatment, there were significant differences in mean BCVA changes (χ2=11.137, 9.746; P＜0.05). Two months after treatment, there were significant differences in CRT changes between BRVO and CRVO groups with different treatment regimens (F=3.960, 3.722; P＜0.01). The time required to improve BCVA by 0.1 logMAR unit in the eyes of BRVO and CRVO combined treatment group was shorter than that in the eyes of BRVO, CRVO DEX treatment group and the BRVO, CRVO ranibizumab treatment group, and the differences were statistically significant (BRVO: Z=－2.687, －3.877; P＜0.05; CRVO: Z=－2.437, －3.575; P＜0.05). The time required for CRT to drop to 300 μm in the CRVO combined treatment group was significantly shorter than that in the CRVO DEX treatment group and the CRVO ranibizumab treatment group, and the difference was statistically significant (F=6.910, P＜0.010); there was no statistically significant difference between the different BRVO treatment groups (F=1.786, P＞0.05). The number of re-treated eyes in the initial combined treatment group and DEX treatment group was less than that in the ranibizumab treatment group, and the difference was statistically significant (χ2=18.330, 7.224; P＜0.05). The retreatment interval of the eyes in the initial combined treatment group was significantly longer than that in the DEX treatment group and the ranibizumab treatment group, and the difference was statistically significant (P＜0.01). There was no significant difference in the incidence of intraocular hypertension among the initial combined treatment group, DEX treatment group and ranibizumab treatment group (χ2=0.058, P＞0.05). ConclusionsThe new strategy of initial combination therapy with DEX and ranibizumab in the treatment of RVO-ME has a better short-term effect. Compared with the monotherapy group, the retreatment interval is shorter, the visual and anatomical benefits are faster, the efficacy lasts longer, and the safety is better.
ObjectiveTo observe the differences in the positive rate of conjunctival sac microbial culture after different methods of preventing infection before intravitreal injection (IVI). MethodsA prospective case-control study. A total of 1 200 participants with fundus diseases who received IVI injection at Tianjin Medical University Eye Hospital from July 2021 to December 2023 were included. Patients were randomly divided into 6 groups according to eye spot with antibiotic solution 3, 1 and 0 days before IVI and local eye disinfection with povidone-iodine (PVI) 3 min and 30 s before IVI: the first 3 days of antibiotics+3 min PVI group, the first 1 day of antibiotics+3 min PVI group, the first 0 days of antibiotics+3 min PVI group, the first 3 days of antibiotics+30 s PVI group, the first 1 day of antibiotics+30 s PVI group, the first 0 days of antibiotics+30 s PVI group, there were 200 cases in each group. Microbial sampling and cultivation of conjunctival sac were conducted before IVI to compare the differences in positive rates among different groups. Multiple group comparisons were conducted using one-way analysis of variance. The comparison of count data is conducted using χ2 test. ResultsAmong the 1 200 patients, there were 566 males and 634 females. Age (62.59±13.44) years old. There were 397 cases of diabetes and 482 cases of hypertension. IVI frequency (2.35±2.34). 64 cases were positive for conjunctival sac culture before IVI. The age (F=1.468), sex composition ratio (χ2=2.876), diabetes (χ2=10.002), hypertension (χ2=6.019), times of IVI (χ2=4.507), and positive rate of conjunctival sac bacterial culture (χ2=6.272) of patients in each group had no statistical significance (P＞0.05). Using the duration of antibiotic application before IVI as a stratified factor, there was no statistically significant difference in the positive rate of conjunctival sac culture between groups with different durations of antibiotic application before IVI [χ2=0.414, P=0.52, combined odds ratio (OR)=0.819, 95% confidence interval (CI) 0.493-1.360]. Using the duration of PVI application as a stratified factor, there was no statistically significant difference in the positive rate of conjunctival sac culture between different PVI disinfection times [χ2=0.000, P=1.000, combined OR=1.00, 95%CI 0.503-1.988]. ConclusionsPre IVI treatment with 0.5% PVI for 30 s can inhibit the growth of microbial colonies in the conjunctival sac. The application of local antibiotic eye fluid in the anterior eye of IVI cannot reduce the positive rate of conjunctival sac bacteria.
Endophthalmitis caused by intravitreal injection is a rare disease which impair patients’s vision. In recent years, with the increase of the diseases and frequency of intravitreal injections, the incidence of endophthalmitis has increased. Standardizing each step of intravitreal injections is an important method to reduce postoperative endophthalmitis. Despite the current availability of prevention strategies providing by a lot of clinical trials, there are considerable variations and a lack of consensus and inconsistencies in clinical practice. Understanding the existing key measures, standardizing the operation of intravitreal injection in my country, and minimizing the incidence of infective endophthalmitis are of positive significance for improving the treatment of ophthalmology, especially fundus diseases.
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.