Previous Anti-vascular Endothelial Growth Factor Research Articles

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

Incidence of Total Blindness After Central Retinal Artery Occlusion With Ocular Neovascularization

Purpose: To determine the time-based incidence of total blindness after central retinal artery occlusion (CRAO) with secondary ocular neovascularization (ONV). Methods: In this retrospective cohort study, electronic records were queried using ICD-9 and ICD-10 codes to identify patients with secondary ONV post-CRAO. Patients with possible alternative ONV etiologies, previous panretinal photocoagulation (PRP), and/or previous antivascular endothelial growth factor (anti-VEGF) therapy were excluded. Clinical data included demographics, medical comorbidities, ONV manifestations, medical/surgical management, and best-corrected visual acuity (BCVA). Kaplan-Meier analysis was performed with total blindness (defined as a BCVA of no light perception) as the outcome of interest. Results: Of 345 eyes with CRAO, 34 met the inclusion criteria with a mean (±SD) follow-up of 22.0 ± 26.2 months. ONV management included PRP (70.6%), glaucoma drainage implant surgery or transscleral cyclophotocoagulation (32.4%), and intravitreal anti-VEGF therapy (mean 2.8 ± 5.6 injections per patient). The cumulative incidence of total blindness was 49.4% (95% confidence interval, 27.2%-71.6%) at 24 months, with 53.3% of cases occurring within 4 months of ONV onset. Conclusions: Post-CRAO ONV is associated with a high risk for progression from severe vision loss to total blindness. Neovascular glaucoma can present up to 4 months after CRAO, challenging the paradigm of “30-day-glaucoma.” Routine gonioscopy should extend through this period, while glaucoma surgery can delay further vision loss. These findings can be used to counsel patients on the importance of follow-up adherence.

Real-world study to evaluate the efficacy and safety of intravitreal brolucizumab for refractory neovascular age-related macular degeneration

This retrospective study evaluated the real-world safety and effectiveness of switching to intravitreal brolucizumab for refractory neovascular age-related macular degeneration (nAMD). A total of 81 patients who received brolucizumab injections as switch therapy were followed for more than 3 months. A good response was defined as better anatomical improvement or extended injection intervals compared with previous anti-vascular endothelial growth factor (VEGF) treatment over a mean follow-up period of 41.4 weeks. Approximately 82.7% of patients showed a good response after switching. After 1 year, patients showed significant visual gains (+ 6.6 letters, p = 0.006) and central retinal thickness reductions (− 112.6 µm, p < 0.001), with 30.8% having injection intervals extended over 12 weeks. In the poor-response group, visual acuity and anatomical outcomes worsened soon after switching. More previous injections, thinner baseline central retina, and the presence of prechoroidal cleft or polypoidal lesion resulted in a better response (p < 0.05). Adverse effects occurred in eight eyes (9.9%), including one retinal vascular occlusion and seven intraocular inflammation cases, which were unrelated to the response. Most patients with nAMD refractory to anti-VEGF treatment demonstrated anatomical improvement or extended injection intervals after switching. This study shows that identified structural biomarkers may predict treatment response and select an appropriate therapeutic strategy.

Efficacy of 190 mcg fluocinolone acetonide intravitreal implant: microperimetry and OCT real-life data.

Fluocinolone acetonide is a valid alternative treatment for patients with chronic diabetic macular edema (DME) with poor response to anti-vascular endothelial growth factor (VEGF) therapy. The purpose of this study is to report the efficacy and safety of ILUVIEN® implant in pseudophakic eyes with persistent DME. This is a single-centre pilot-study of 8 patients with persistent DME treated with the ILUVIEN implant, despite previous anti-vascular endothelial growth factor and/or steroid treatment. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) central retinal thickness, intraocular pressure (IOP) and microperimetric data were evaluated at baseline and month 1, 3 and 6 post treatment. All data are presented as mean and standard deviation. At baseline, 1, 3 and 6 months, we had BCVA of 0.26±0.22, 0.38±0.27, 0.48±0.27 and 0.46±0.24; IOP of 15.00±2.67, 15.50±3.16, 14.88±2.42 and 15.63±2.67 mmHg; macular thickness of 652±231, 487±278, 475±287 and 413±211 µm; macular sensitivity of 6.83±4.20, 6.13±3.72, 7.68±3.40 and 7.71±3.33 dB; bivariate contour elliptic area (BCEA) 95.4% 3.8±3.42, 6.06±10.06, 3.05±2.46 and 2.59±2.19°2. According to the results of our study, fluocinolone acetonide (FAc) is a valid therapy option despite some limitations. It has been evidenced that FAc is more effective in patients with mild central macular thickening, while in those with modest to severe central macular thickness (CMT), different therapy strategies should be considered.

Morphological Macular Changes Under Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration Refractory to Previous Anti-VEGF Treatment Compared with Treatment-Naive Eyes.

To evaluate the morphological macular changes and fluid dynamics under brolucizumab treatment in eyes refractory to previous anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) compared with treatment-naive eyes. Retrospective study of all eyes treated with brolucizumab for nAMD between 2020 and 2021 with a fixed injection regimen and one year follow-up. Treatment-naive eyes (TN) were compared with eyes refractory to previous treatment with bevacizumab, ranibizumab, or aflibercept (RT). The primary outcome measure was change of best-corrected visual acuity (BCVA). Secondary outcome measures included foveal central thickness (FCT), presence of intra- or subretinal fluid (IRF, SRF) and presence of pigment epithelial detachment (PED) at any time point during treatment in both groups. Seventeen TN eyes and 17 RT eyes were included. Mean BCVA and mean FCT in TN eyes had significantly improved after 3 months and continued to improve during treatment (p<0.05 and p=0.001, respectively). In RT eyes, mean BCVA did not change significantly while mean FCT had improved after 3 months of treatment and remained stable thereafter. SRF or PED were more frequent in RT eyes compared with TN eyes (p=0.003 and p=0.005, respectively). After 3 months of treatment, the BCVA increased significantly only in TN eyes, while the FCT was significantly reduced in both groups. IRF appears to be similarly seen in both groups after the loading phase; however, SRF and PED appear to be more frequent in the RT eyes compared with TN eyes.

PREDICTING LESION SHRINKAGE IN EYES WITH MYOPIC CHOROIDAL NEOVASCULARIZATION FROM FEATURES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To identify baseline morphological predictors of lesion shrinkage in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor. This retrospective study included 46 eyes (41 consecutive patients) with active mCNV receiving anti-vascular endothelial growth factor treatment. Optical coherence tomography angiography was performed at baseline and 1 year after treatment. Quantitative features were obtained from optical coherence tomography angiography images using AngioTool software. Eyes were classified as "high shrinkage" or "low shrinkage" according to the median relative change in lesion area. Baseline quantitative morphological features associated with mCNV shrinkage were identified in univariate and multivariate analyses. The mCNV area was significantly smaller after 1 year ( P = 0.013), with a median relative change of -16.5%. The relative change in mCNV area was -48.3% in high-shrinkage eyes (n = 23) and -5.2% in low-shrinkage eyes (n = 23). High-shrinkage eyes had a smaller mCNV area ( P = 0.013), shorter total vessel length ( P = 0.023), and higher end point density ( P < 0.001). Multivariate analysis showed significant associations of high shrinkage with end point density (β = -0.037, P = 0.043) and previous anti-vascular endothelial growth factor treatment (β = 0.216, P = 0.029). Morphological features of neovascularization detected by optical coherence tomography angiography can predict lesion shrinkage in eyes with mCNV receiving anti-vascular endothelial growth factor therapy. Higher end point density contributed to shrinkage, particularly of treatment-naive lesions.

The effect of intravitreal dexamethasone implantation on diabetic macular edema refractory to anti-vascular endothelial growth factor treatment

ABSTRACT Purpose To evaluate the efficacy and safety of intravitreal dexamethasone (DEX) implantation for diabetic macular edema (DME) that proved unresponsive to previous anti-vascular endothelial growth factor (VEGF) treatment. Methods This prospective interventional study recruited 91 patients with refractory DME after previous anti-VEGF treatments in one or both eyes. All patients were followed up for at least 12 months. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and macular volume were measured. Results Over the 12 months, a mean of 2.1 ± 0.8 DEX implantations were administered per eye; 26 eyes (28.9%) received 1 implantation, 31 (34.4%) received 2, and 34 (36.7%) received 3. BCVA was significantly improved in the first 6 months, from 54.8 to 59.5 letters. Both CST and macular volume decreased significantly after DEX implantation and maintained these improvements for at least 12 months. Subjects who needed the second DEX implantation had a greater number of prior anti-VEGF injections than did those who needed only one implantation (6.0 vs 3.0). Conclusions Two-thirds of refractory DME required less than two DEX implantations to maintain a dry macula for 12 months. Early switching to intravitreal DEX can be considered as the second-line therapeutic option, especially during the COVID-19 pandemic.

Effect of Supra-Choroidal Triamcinolone Injection on Best-Corrected Visual Acuity and Central Retinal Thickness in Patients with Macular Edema Secondary to Retinal Vein Occlusion

Purpose: To find out the effect of suprachoroidal Triamcinolone injection on best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with macular edema secondary to retinal vein occlusion. Study Design: Interventional case series. Place and Duration of Study: College of Ophthalmology and Allied vision Sciences, Ophthalmology department, Unit II Mayo hospital, Lahore, from September 2019 to January 2020. Methods: This study included 45 patients diagnosed with unilateral, retinal vein occlusion associated with macular edema. Patients with previous anti-vascular endothelial growth factor injection or any steroid injection received in the last 3 months or macular edema due to any other cause were excluded from the study. Only one eye of each patient was enrolled. The patients were treated with suprachoroidal triamcinolone injection (4 mg/100µL concentration). Patients with baseline central retinal thickness (CRT) of &gt; 300 µm were included in the study. Serial changes in this parameter were evaluated at 1 week, 1 month and 3?months after suprachoroidal triamcinolone injection. Final CRT and Best-corrected visual acuity (BCVA) was recorded after three months. Results: Out of 45 patients, 26 (57.7%) were males and 19 (42.2%) were females. Majority of the patients (35.4%) were 51–60 years old. During first week the visual acuity was 0.321 ± 0.273 LogMAR, after one month it was 0.468 ± 0.291 and 0.406 ± 0.318 after 03 months with a p value of 0.003. After three months significant decrease in CRT was observed. With a p-value of 0.002. Conclusions: Suprachoroidal injection significantly improves BCVA and decreases CRT in patients with macular edema due to retinal vein Occlusion. Keywords: Retinal vein occlusion, suprachoroidal injection, triamcinolone acetonide.

Comparison of Anatomical and Functional Outcomes of Intravitreal Dexamethasone Implant between Phakic and Pseudophakic Eyes with Diabetic Macular Edema

Purpose To compare the effectiveness of dexamethasone (DEX) intravitreal implants for the treatment of diabetic macular edema between phakic and pseudophakic eyes after a follow-up.Methods A total of 79 eyes in 79 patients with diabetic macular edema who were insufficiently responsive to the previous anti-vascular endothelial growth factor treatment and applied intravitreal DEX implant were included in this retrospective study. The patients were divided into two groups according to their type of lenses: pseudophakic (group 1) and phakic (group 2). Best-corrected visual acuity, intraocular pressure (IOP), retinal nerve fiber layer thickness, and central macular thickness changes in the two groups were compared.Results Group 1 comprised 42 eyes in 42 patients with a mean age of 64.02 ± 3.79 years, while group 2 comprised 37 eyes in 37 patients with a mean age of 64.19 ± 5.08 years. In both groups, best-corrected visual acuity improved significantly with a significant decrease in central macular thickness (p < 0.001). In both lens types, the IOP values decreased significantly on the first day but subsequently increased significantly compared to baseline from one week to six months. Increases in IOP values were significantly higher in group 1 at the first week, 1st month, and 6th month compared with group 2. During follow-up, the inferior quadrant retinal nerve fiber layer showed a significant decrease in both groups.ConclusionsIn both phakic and pseudophakic eyes, intravitreal DEX implantation is an effective treatment method with low-risk complications. In our study, the pseudophakic group experienced a significantly earlier increase in IOP and at higher levels than did the phakic group. In light of these data, we suggest that in patients with pseudophakic eyes, follow-ups for IOP should be stricter and started earlier after intravitreal DEX treatment.

The long-term efficacy and safety of fluocinolone acetonide intravitreal implant 190 μg (ILUVIEN®) in diabetic macular oedema in a multi-ethnic inner-city population.

The purpose of this study is to report the long-term efficacy and safety of 0.19 mg fluocinolone acetonide intravitreal implant (ILUVIEN®) in pseudophakic eyes with diabetic macular oedema in a multi-ethnic patient cohort. This is a single-centre retrospective analysis of patients with persistent diabetic macular oedema, despite previous anti-vascular endothelial growth factor and/or steroid treatment, treated with the ILUVIEN implant according to national guidelines. Patients with follow-up of less than 24 months were excluded. Best corrected visual acuity, central retinal thickness and intraocular pressure were evaluated at baseline and month 3, 12, 24 and 36 post-treatment. A sub-group analysis was performed on eyes with 36-month follow-up data. In total, 24 eyes (24 patients) completed at least 24 months of follow-up, of which 9 completed 36 months of follow-up. Three-fourths of the patients were black or South Asian (blacks, Asians and minority ethnic). Improvement in mean best corrected visual acuity was seen at year 1 and year 3 improving from 0.62 LogMAR at baseline to 0.55 LogMAR at year 1 and 0.47 LogMAR at year 3 (all p > 0.05). Mean central retinal thickness also showed a progressive reduction from 471 μm at baseline to 397 μm at year 1 and 339 μm at year 3 (all p < 0.05). Four eyes required intraocular pressure-lowering drops post-implant. Supplementary treatment for persistent or recurrent diabetic macular oedema was necessary in 13 eyes over the total study period of 3 years. Blacks, Asians and minority ethnic patients had a worse response compared with white patients. The ILUVIEN implant was effective and safe in the treatment of multi-ethnic patients with diabetic macular oedema refractory to conventional therapies, improving the vision and macular anatomy, without significant adverse events up to 36 months post-treatment.

Effects of Switching to Aflibercept in Treatment Resistant Macular Edema Secondary to Retinal Vein Occlusion.

Purpose:The aim of this study was to examine 12-month outcomes of eyes switched from intravitreal ranibizumab or bevacizumab to aflibercept for cystoid macular edema due to retinal vein occlusion (RVO).Design:Retrospective, observation, case series.Methods:A retrospective study was performed assessing eyes with RVO switched to aflibercept for at least 12 months. To be included in the study, eyes had to have macular edema despite treatment for at least 6 months with bevacizumab and/or ranibizumab before the switch, central foveal thickness (CFT) ≥300 μm at time of switch, and visual acuity (VA) ≤60 early treatment of diabetic retinopathy score (ETDRS) letters (20/40 Snellen equivalent). Outcome measures included change in VA (in ETDRS letters), CFT, and interval between intravitreal injections.Results:27 eyes of 27 patients were included in the analysis: 13 with branch RVO, and 14 with central RVO. Mean VA before switch was 54.2 ± 23.7 letters (20/80 Snellen equivalent) and mean CFT was 460.4 ± 178.2 μm. Mean number of previous anti-vascular endothelial growth factor (VEGF) injections was 29.5 ± 19.2. At 12 months, mean VA improved by 8.7 ± 13.2 letters (P < 0.01) and mean CFT decreased by 180.9 ± 207.7 μm compared with baseline (P < 0.01). Mean injection interval increased by 1.6 ± 2.0 weeks to 6.9 ± 1.2 weeks, but this was not statistically significant (P = 0.18).Conclusions:In our small retrospective study, eyes switched to intravitreal aflibercept for persistent cystoid macular edema (CME) due to RVO improved vision and macular thickness; however, larger prospective studies are required to validate our findings.

Prognostic factors for combined ranibizumab and prompt verteporfin photodynamic therapy for polypoidal choroidal vasculopathy.

To investigate the prognostic factors for the combined therapy of ranibizumab and prompt verteporfin photodynamic therapy (vPDT) for eyes with polypoidal choroidal vasculopathy (PCV). Sixty-two PCV eyes of 62 patients that received the initial treatment of intravitreal ranibizumab followed by vPDT within 1 week plus a 2nd intravitreal ranibizumab 1 month later in one single medical center were retrospectively enrolled. Best-corrected visual acuity (BCVA) and parameters obtained from optical coherence tomography at baseline, 3 months, 6 months and 1 year were measured and compared. Factors associated with polyp regression, recurrent hemorrhage and visual improvement were analyzed. After the loading treatment, complete and partial polyp regression was achieved in 53.6% and 39.3% of cases, respectively at Month 3. The mean logarithm of the minimum angle of resolution of BCVA improved from 0.64 ± 0.38 to 0.55 ± 0.46 (P = 0.008) at Month 12. Recurrent hemorrhage (P = 0.001) and previous anti-vascular endothelial growth factor (VEGF) treatment (P = 0.017) were associated with poorer visual improvement at Month 12. Incomplete polyp regression (P = 0.038) and previous anti-VEGF treatment (P = 0.005) were associated with a higher risk of recurrent hemorrhage. Recurrent hemorrhage was associated with poor visual improvement after combined ranibizumab and vPDT for PCV. Complete polyp eradication was associated with a lower risk of recurrent hemorrhage. Patients who had previously received anti-VEGF were associated with recurrent hemorrhage and poor visual improvement; more frequent follow-ups and more aggressive subsequent treatments may be needed for these cases.

Predictive factors for patients receiving intravitreal anti-vascular endothelial growth factor for the treatment of diabetic macular edema

To determine whether anemia and other demographic or laboratory "risk factors" impact anti-vascular endothelial growth factor treatment in diabetic macular edema patients. This is a retrospective, time-varying cohort study using a medical claims database to identify new diabetic macular edema patients who had received at least one intravitreal injection of anti-vascular endothelial growth factor. Exclusion occurred for having <2 years in the plan prior to diabetic macular edema diagnosis, any history of proliferative retinopathy or any treatment that is used for diabetic macular edema. Covariates of interest were demographic characteristics, laboratory values, and clinical factors such as previous anti-vascular endothelial growth factor used, number of involved eyes, year of treatment, and time since last injection. Those variables that changed with time were assessed and updated at each visit. The main outcome measure was the odds of receiving treatment at any visit. In total, 189 new diabetic macular edema patients with follow-up were analyzed, covering 729 visits with 543 (74.5%) receiving treatment. Univariate analysis showed that male gender (odds ratio: 0.54, 95% confidence interval: 0.32-0.91, p = 0.03), every week since last injection (odds ratio: 0.94, 95% confidence interval: 0.91-0.97, p = 0.001), and having two eyes affected (odds ratio: 2.09, 95% confidence interval: 1.10-3.97, p = 0.02) were associated with getting an injection. After multivariate analysis, only time since previous injection with every week that passed reduced the odds on having an injection at the next visit (odds ratio: 0.95, 95% confidence interval: 0.92-0.97, p < 0.001). Anemia was not associated with receiving an injection (odds ratio: 1.05, 95% confidence interval: 0.61-1.80, p = 0.86). This study used time-varying methodology to better identify which patients will likely need an injection at any one visit. While anemia was not found to impact injections, our results can aid future endeavors that may incorporate clinical visit information in developing a full prediction model to help make diabetic macular edema care more efficient.

Switching to Aflibercept in Diabetic Macular Edema after Unsatisfactory Response to Other Anti-vascular Endothelial Growth Factor Drugs.

PurposeTo evaluate the efficacy of switching to aflibercept in diabetic macular edema (DME) with suboptimal response to previous anti-vascular endothelial growth factor (anti-VEGF) injections.MethodsA prospective interventional case series study recruited patients from a single center diagnosed with DME with suboptimal response to anti-VEGF injections. Three consecutive monthly injections of aflibercept were performed. The primary outcome measure was mean change in visual acuity after switching to aflibercept.ResultsForty-two patients (42 eyes) were included. Baseline logarithm of the minimum angle of resolution (logMAR) visual acuity was 0.87 ± 0.23 and improved significantly to 0.62 ± 0.29, 0.56 ± 0.34, and 0.46 ± 0.35 at 1, 2, and 3 months, respectively, after the first injection. Mean baseline retinal thickness was 451.57 ± 107.09 µm and decreased significantly at 1, 2, and 3 months after switching to aflibercept (346.52 ± 79.03, 328.24 ± 81.98, and 313.71 ± 85.79 µm, respectively). Both visual improvement and mean change in retinal thickness were significant in patients with pre-aflibercept best-corrected visual acuity less than 1.0 logMAR but were not significant in patients with best-corrected visual acuity more than 1.0 logMAR.ConclusionsSwitching to aflibercept in DME patients with an unsatisfactory response to previous anti-VEGF injections provided acceptable short-term visual and retinal architectural improvement.

EFFICACY AND FREQUENCY OF INTRAVITREAL AFLIBERCEPT VERSUS BEVACIZUMAB FOR MACULAR EDEMA SECONDARY TO CENTRAL RETINAL VEIN OCCLUSION.

To compare the safety, efficacy, and frequency of intravitreal injection of aflibercept and bevacizumab for treatment of macular edema secondary to central retinal vein occlusion. Prospective, comparative, randomized, interventional study. Eyes with macular edema secondary to central retinal vein occlusion were randomized between two groups according to the intravitreal injection used. Group A included eyes treated with intravitreal aflibercept, and Group B included eyes treated with intravitreal bevacizumab injections. The inclusion criteria were macular edema secondary to central retinal vein occlusion and follow-up duration of at least 12 months after the first injection. Exclusion criteria were macular ischemia, associated diabetes, hypertensive or renal retinopathy, other retinal disease, and previous anti-vascular endothelial growth factor injection. The main outcome measures are central foveal thickness, best-corrected visual acuity, time intervals between injections, improved retinal nonperfusion, and any reported complication. Group A included 39 patients with a mean age of 57.4 ± 8.2 years. Group B included 40 eyes with a mean age of 56.5 ± 9.1 years. Twelve months after the first injection, central foveal thickness significantly improved from 475.45 ± 71.05 m to 259.11 ± 20.67 m in Group A and from 460.22 ± 89.38 m to 264.29 ± 32.05 m in Group B; best-corrected visual acuity significantly improved from 0.81 ± 0.16 logarithm of the minimum angle of resolution (20/125) to 0.34 ± 0.14 logarithm of the minimum angle of resolution (20/40) in Group A and from 0.73 ± 0.15 logarithm of the minimum angle of resolution (20/100) to 0.33 ± 0.17 logarithm of the minimum angle of resolution (20/40) in Group B; the mean number of injections was 3.72 ± 2.93 in Group A and was 5.44 ± 2.85 in Group B (P < 0.05); and the mean interval between injections was 54.23 ± 8.47 days in Group A and was 35.12 ± 7.76 days in Group B (P < 0.05). Retinal nonperfusion improved in 9/12 eyes in Group A and in 3/8 eyes in Group B (P < 0.05). Both aflibercept and bevacizumab are comparably effective for treatment of macular edema secondary to central retinal vein occlusion without significant complications. However, the burden of frequent intravitreal injections could be significantly reduced when using aflibercept.

Dexamethasone Intravitreal Implant in Diabetic Macular Edema: Real-Life Data from a Prospective Study and Predictive Factors for Visual Outcome.

IntroductionThe purpose of the study was to evaluate the long-term anatomical and functional outcomes in patients with diabetic macular edema (DME) treated with intravitreal dexamethasone implant and to determine the predictive factors for the final visual outcome.MethodsThe study included 54 patients with DME refractory to previous antivascular endothelial growth factor (anti-VEGF) who were treated with intravitreal dexamethasone implant. Predictive factors for visual outcome were assessed. In addition, the change in best-corrected visual acuity (BCVA) and the percentage of patients with edema resolution were evaluated.ResultsAt the end of the 12-month follow-up, patients with DME gained + 5.2 letters (about 1 Snellen line), while 57.4% of patients presented total resolution of macular edema. Negative predictive factors for the final visual outcome were found to be increasing age, increasing macular thickness, phakic status, the presence of intraretinal fluid, hyperreflective foci, hard exudates, as well as external limiting membrane and ellipsoid zone disruption. The mean number of injections was 2.1.ConclusionsThe various predictive factors that determine the visual outcome and possibly define patient prognosis after dexamethasone intravitreal implant in DME cases have been studied. The long follow-up showed that dexamethasone intravitreal implant seems to be a safe and effective treatment for this disease, requiring a limited number of injections.

Safety and Efficacy of Ziv-Aflibercept in the Treatment of Refractory Diabetic Macular Edema.

To evaluate the safety and efficacy of ziv-aflibercept (Zaltrap; Sanofi-Aventis, Bridgewater, NJ/Regeneron Pharmaceuticals, Tarrytown, NY) in the treatment of refractory diabetic macular edema (DME). Retrospective case series looking at the safety of ziv-aflibercept in patients with DME refractory to previous anti-vascular endothelial growth factor (VEGF) therapy. Detailed ophthalmologic examination, best-corrected visual acuity, and optical coherence tomography measurements were performed pre-switch, as well as at each monthly follow-up visit. The study included 34 eyes of 26 patients. The mean number of ziv-aflibercept injections post-switch was 2.03 injections. Visual acuity improved from a mean of 0.63 logMAR pre-switch to 0.51 logMAR after the first visit and 0.46 logMAR after the second visit post-switch (P < .084). Macular thickness improved from a mean of 513.79 μm to 411.79 μm (P = .006) on the first visit and 426.76 μm (P = .029) after the second visit post-switch. No adverse ocular or systemic side effects were reported on any of the follow visits. Ziv-aflibercept appears to be safe and effective in patients with refractory DME previously treated with other anti-VEGF agents in the short term. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:399-405.].

Switching to aflibercept among patients with treatment-resistant neovascular age-related macular degeneration: a systematic review with meta-analysis.

PurposeTo systematically review anatomical and functional outcomes subsequent to switching from bevacizumab/ranibizumab to aflibercept monotherapy in patients with treatment-resistant neovascular age-related macular degeneration (nAMD).DesignSystematic review and meta-analysis.MethodsMedline, PubMed, Embase, and Cochrane databases were searched up to July 2016 for available scientific literature which met inclusion criteria. Eligible studies reported visual and anatomical outcomes with at least 6 months of follow-up among patients with nAMD and persistent or resistant exudative fluid despite previous anti-vascular endothelial growth factor (VEGF) therapy (bevacizumab and/or ranibizumab) and were switched to aflibercept monotherapy. Mean changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were pooled using random-effects models with 95% confidence intervals (CIs).ResultsOf 82 papers reviewed, 28 studies met inclusion criteria of this review. Pooled results showed a small mean improvement in BCVA at 6 and 12 months following switching (1.11 letters, 95% CI −0.25 to 2.46, P=0.17 and 0.63 letters, 95% CI −0.26 to 1.52, P=0.17, respectively). There was a significant improvement in mean CRT following switching (−61.90 µm, 95% CI −77.10 to −46.80, P<0.001 and −50.00 µm, 95% CI −63.20 to −36.80, P<0.001 at 6 and 12 months, respectively).ConclusionPooled analysis demonstrated significantly improved anatomical outcomes; however, visual function remained stable, having a comparable effect to other anti-VEGF agents in preservation of vision. These patients had poorly responsive chronic disease with limited potential for visual recovery. Switching to aflibercept with frequent monitoring may be a suitable option for patients who have developed treatment resistance.

Short-term effect of aflibercept on visual acuity and central macular thickness in patients not responding to ranibizumab and bevacizumab

To analyze the clinical outcome of treatment with aflibercept in patients not responding to ranibizumab and bevacizumab. Retrospective review of 32eyes from 30consecutive patients with choroidal neovascularization (CNV) who showed no response to treatment with ranibizumab or bevacizumab and were switched to aflibercept. Visual acuity, central macular thickness (CMT) and presence or absence of intraretinal or subretinal fluid were analyzed before switching to aflibercept, after each of three uploading dose injections of aflibercept and 6, 8 and 10weeks after the third aflibercept injection. All eyes had previous ranibizumab injections and the mean number of previous injections was 14.75 (±7.38). Mean duration of previous anti-vascular endothelial growth factor (VEGF) treatment was 38months (±27.35 months). Mean visual acuity before switching to aflibercept was 0.40±0.30logMAR. After the third injection visual acuity was 0.3±0.3logMAR and 10weeks after the third injection it was 0.50±0.20logMAR. No significant differences were seen during treatment and follow-up. The mean CMT was 394±118µm at baseline, at follow-up (first, second and third, group week6, group week8 and group week10) it was 317±108µm, 301±99µm, 292±83µm, 270±78µm, 340±146µm and 377±92µm, respectively. Significant reductions in CMT were seen between the first and third follow-up injections and at group week 8. Of the patients 59.4 % were complete non-responders to aflibercept. Aflibercept results in improvement in CMT in non-responders to ranibizumab and bevacizumab as long as therapy is given continuously and can therefore be an alternative therapy.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward.

The recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases. We reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described. We reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. Analysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.