Multiple Anti-vascular Endothelial Growth Factor Research Articles

Switching to ziv-aflibercept in resistant diabetic macular edema non responsive to ranibizumab injection

BackgroundDiabetic macular edema (DME) is a leading cause of visual loss in diabetic patients and is managed using multiple anti-vascular endothelial growth factor (VEGF) agents such as bevacizumab, ranibizumab and aflibercept. The present study evaluates effectiveness of intravitreal injection of ziv-aflibercept in resistant diabetic macular edema.MethodsThis is a prospective interventional study that was carried out on 59 eyes of 40 diabetic patients with diabetic macular edema resistant to three prior consecutive ranibizumab injections. On all patients, thorough ophthalmic evaluation including optical coherence tomography was performed. In patients with persistent intraretinal or subretinal fluid, ziv- aflibercept 1.25 mg (0.05 ml) was administered by intravitreal injection monthly during the 6 month study period from June to December 2019.ResultsThe central macular thickness (CMT) decreased significantly from 395.08 ± 129.9 um at baseline to 282.39 ± 95.278, 245.36 ± 79.861 and 201.17 ± 54.042 after 1, 3 and 6 months of treatment respectively (p < 0.001). Best corrected visual acuity (BCVA) in log MAR units was significantly improved from 0.95 ± 0.21 to 0.51 ± 0.23 after 6 months (p = 0.001). After treatment, negative correlations were detected between age, number of injections, duration of DM and level of glycated hemoglobin (HbA1c) and variation of both CMT and BCVA. The only significant predictor for low final CMT after 6 months of injection was the CMT after 3 months of injection (p = 0.001).ConclusionZiv-aflibercept is a highly effective and safe drug in cases of DME resistant to previous ranibizumab injections especially in low-income countries.Trial registrationThis study was retrospectively registered at clinicaltrials.gov (ID: NCT04290195) on 28-2-2020.

Sequential Short Interval Anti-VEGF for the Treatment of Stage 4 Retinopathy of Prematurity.

A 23-month-old girl born at 23 weeks' gestational age with a birth weight of 453 g and retinopathy of prematurity (ROP) stage 4A in 360° and plus disease in both eyes was treated in another institution with laser; her treatment was complicated with two cardiac arrests during the procedure. The patient was referred and treated at 31 weeks with repeated intravitreal bevacizumab injection in both eyes secondary to progressive ROP. Treatment with multiple anti-vascular endothelial growth factor (VEGF) therapy as monotherapy led to the resolution of a retinal detachment and full vascularization of the retina in both eyes. To the best of the authors' knowledge, this is the first description of a patient with stage 4A ROP treated solely with anti-VEGF after failed laser treatment that led to complete resolution of a retinal detachment without surgical intervention. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:159-163.].

Changes in the Foveal Avascular Zone Area and Retinal Vessel Density after Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration

ABSTRACT Purpose To investigate changes in the foveal avascular zone (FAZ) area and retinal vessel density (VD) in the macula of patients receiving multiple anti-vascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (N-AMD). Methods This study included 54 eyes of 54 treatment-naïve N-AMD patients. Thirty-three eyes were treated with intravitreal aflibercept injections, and 21 eyes were treated with intravitreal ranibizumab injections. Unaffected fellow eyes (54 eyes) were used as controls. All image scans were acquired after the macular architecture had recovered with drying up of the subretinal fluid/hemorrhage after treatment. Results Both the superficial and deep FAZ areas were significantly larger in the aflibercept group than in the control group. The VD was also significantly reduced in the aflibercept group. Conclusions Prolonged and repeated anti-VEGF therapy may cause an increase in the FAZ area and a decrease in the VD in patients with N-AMD, indicating ischemic damage.

Prediction of Anti-VEGF Response in Diabetic Macular Edema After 1 Injection.

With multiple anti-vascular endothelial growth factor and steroid therapies available for diabetic macular edema (DME), there is a need for early determination of the best treatment for a particular patient to prevent irreversible vision loss from chronic DME. In this study, we classify patients as responders or non-responders to anti-vascular endothelial growth factor (VEGF) monotherapy in the treatment of DME after a single anti-VEGF injection. The study was designed as a single center, retrospective, interventional case series. We included patients who received 3 consecutive monthly injections with the same anti-VEGF agent. We excluded patients who were treated for DME in the preceding 3 months with any form of anti-VEGF therapy. Visual acuity and central retinal thickness (CRT) data were followed for one year. Receiver operating characteristic (ROC) curve analysis was performed in order to identify cutoff values for identifying responders. 107 eyes were reviewed, with 40 eyes of 34 patients meeting all inclusion criteria. Based on ROC curve analysis, a reduction in CRT by > 15% at 1-month, identified eyes that responded to treatment and had a >25% reduction in CRT at 3-months (sensitivity 0.75, specificity 0.92). DME eyes that have early response to anti-VEGF treatment by reduction in CRT will have significant response to treatment by 3 months.

Dexamethasone implant in retinal vein occlusions.

Dear editor We read the article entitled “Therapeutic effect of dexamethasone implant in retinal vein occlusions resistant to anti-VEGF therapy” by Wallsh et al with great interest.1 The authors investigated the efficacy of the intravitreal dexamethasone (DEX) implant in patients with retinal vein occlusions (RVOs) who have failed multiple anti-vascular endothelial growth factor (anti-VEGF) injections. They concluded that DEX should be considered as a treatment option in patients with RVOs who have failed anti-VEGF therapy. We congratulate the authors for this well-organized study, and would like to contribute to their findings. Compared with anti-VEGF therapies, DEX implant can reduce the number of injections in patients with RVOs. In patients with macular edema-associated RVOs not responsive to repetitive anti-VEGF therapies, the treatment effect after DEX implant treatment is encouraging. However, these results are achieved at the expense of adverse effects typically associated with steroids: Recent study demonstrated that intravitreal injection of DEX implant was associated with ocular hypertension in 32.6% of the eyes.2 Previous glaucoma and ocular hypertension are risk factors for this increase. Thus, careful monitoring of intraocular pressure is very important to receive DEX implant in patients with RVOs. In addition, phakic patients have to expect cataract progression, with the need for cataract surgery within several years.

Therapeutic effect of dexamethasone implant in retinal vein occlusions resistant to anti-VEGF therapy.

PurposeTo test the efficacy of the intravitreal dexamethasone (DEX) implant in patients with retinal vein occlusions (RVOs) who have failed multiple anti-vascular endothelial growth factor (anti-VEGF) treatments.MethodsA randomized exploratory study of ten patients with branch RVO or central RVO who received at least two previous anti-VEGF treatments and had persistent or unresponsive cystoid macular edema. Treatment with the DEX implant was either every 4 months or pro re nata (PRN) depending on their group assignment for 1 year. Multifocal electroretinography and microperimetry were the primary end points, with high-resolution optical coherence tomography and best-corrected visual acuity as the secondary end points.ResultsAll patients in both the every 4 month and PRN cohorts who completed the study received the three maximal injections of DEX; therefore, the data from both cohorts were combined and reported as a case series. On average, the multifocal electroretinography amplitude increased significantly from 5.11±0.66 to 24.19±5.30 nV/deg2 at 12 months (P<0.005), mean macular sensitivity increased from 7.67±2.10 to 8.01±1.98 dB at 4 months (P=0.32), best-corrected visual acuity increased significantly from 51.0±5.1 to 55.4±5.1 early treatment of diabetic retinopathy study letters at 2 months (P<0.05), and central retinal thickness decreased from 427.6±39.5 to 367.1±37.8 μm at 4 months (P<0.05). Intraocular pressure increased significantly in one patient, with that patient requiring an additional glaucoma medication for management. Additionally, cataract progression increased significantly (P<0.05) in this patient population and partially limited analysis of other end points.ConclusionDEX should be considered as a treatment option in patients with RVOs who have failed anti-VEGF therapy, as the results of this study demonstrated an improvement in retinal morphology and macular function. Cataract progression did occur following multiple consecutive injections; however, steroid-induced glaucoma was not a limiting factor.

A 12-MONTH, SINGLE-MASKED, RANDOMIZED CONTROLLED STUDY OF EYES WITH PERSISTENT DIABETIC MACULAR EDEMA AFTER MULTIPLE ANTI-VEGF INJECTIONS TO ASSESS THE EFFICACY OF THE DEXAMETHASONE-DELAYED DELIVERY SYSTEM AS AN ADJUNCT TO BEVACIZUMAB COMPARED WITH CONTINUED BEVACIZUMAB MONOTHERAPY.

To determine whether a dexamethasone intravitreal implant 0.7 mg (dexamethasone delivery system [DDS], Ozurdex) combined with bevacizumab 1.25 mg (Avastin) provides greater benefit than bevacizumab monotherapy in eyes with diabetic macular edema with incomplete response to multiple antivascular endothelial growth factor injections. Eyes with diabetic macular edema were randomly assigned to receive combination therapy (bevacizumab plus DDS) or bevacizumab monotherapy. Combination therapy eyes received intravitreal bevacizumab at baseline, DDS at Month 1, and subsequent DDS (at Months 5 and 9), whereas monotherapy eyes received bevacizumab (monthly) if indicated. Eyes were eligible for retreatment if the central subfield thickness measured >250 μm, and Early Treatment of Diabetic Retinopathy Study visual acuity was <80 letters (20/25). Forty eyes of 30 patients were enrolled. The mean visual acuity changes from baseline to 12 months were similar in the 2 groups (combined: +5.4 letters; bevacizumab: +4.9 letters; difference = 0.2 letters, 95% confidence interval = -5.9 to 6.3; P = 0.75). The mean reduction in central subfield thickness was greater in the combination group (-45 μm vs. -30 μm, difference = 69 μm, 95% confidence interval = 9-129; P = 0.03) and more patients in the combination group had central subfield thickness <250 μm. The combined treatment group received three fewer supplemental injections of bevacizumab, but this was counterbalanced by the need for an average of 2.1 DDS injections. The dexamethasone implant combined with bevacizumab significantly improves visual acuity and significantly improves macular morphology in eyes with refractory diabetic macular edema, although visual acuity changes are not superior to continued bevacizumab monotherapy.