Anti-vascular Endothelial Growth Factor Drugs Research Articles

Effects of antivascular endothelial growth factor drug treatment on changes in vitreomacular interface, intraocular pressure and visual acuity of patients with age-related macular degeneration.

article: Effects of anti-vascular endothelial growth factor drug treatment on changes in vitreomacular interface, intraocular pressure and visual acuity of patients with age-related macular degeneration - Minerva Medica 2022 Mar 25 - Minerva Medica - Journals

Anti-vascular endothelial growth factor (VEGF) drugs compared to laser photocoagulation for treatment of type 1 retinopathy of prematurity

INTRODUCCIÓN La retinopatía del prematuro es una patología que afecta a recién nacidos de pretérmino, siendo la segunda causa de ceguera infantil a nivel mundial. Los tratamientos más utilizados son la crioterapia o la fotocoagulación láser, pero en el último tiempo, los fármacos anti factor del crecimiento vascular endotelial (anti-VEGF) gradualmente han ganado más adeptos, principalmente en el tratamiento de pacientes con retinopatía del prematuro tipo 1 (ET-ROP). Por lo anterior, es importante realizar un resumen de la evidencia existente para evaluar la eficacia y seguridad de los fármacos anti-VEGF en retinopatía del prematuro tipo 1. MÉTODOS Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metaanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos seis revisiones sistemáticas que en conjunto incluyeron 15 estudios primarios, de los cuales cinco corresponden a ensayos aleatorizados. Concluimos que el uso de anti-VEGF en comparación con la fotocoagulación con láser, probablemente disminuye el riesgo de errores refractivos. Por otro lado, el uso de anti-VEGF podría resultar en poca o nula diferencia en la mortalidad al alta hospitalaria, opacidad de cristalino o córnea que requiera cirugía y desprendimiento completo o parcial de retina, pero la certeza de la evidencia es baja. Finalmente, no es posible establecer con claridad si los anti-VEGF comparados con la fotocoagulación láser aumenta la recurrencia de la retinopatía del prematuro, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

Creation of a neovascular age-related macular degeneration national database using a web-based platform: Fight Retinal Blindness Spain. Report 1: Visual outcomes.

To study the visual outcomes of neovascular AMD (nAMD) treated with anti-vascular endothelial growth factor (VEGF) drugs at national level. Multicenter national database of nAMD eyes treated with anti-VEGF intravitreal injections (ranibizumab, aflibercept, bevacizumab) in fixed bimonthly (FB) or treat-and-extend (TAE) regimens. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) ETDRS letters at baseline and subsequent visits, number of injections and visits data were collected using a validated web-based tool (Fight Retinal Blindness!). 1273 eyes (1014 patients) were included, 971 treatment naïve (TN) and 302 previously treated (PT). Baseline VA (mean ± SD) was 57.5 (±19.5) and 62.2 (±17) (p > 0.001), and 24 months final VA was 60.4 (±21.2) and 58.8 (±21.1) (p=0.326), respectively. Mean VA change at 12/24 months was +4.2/+2.9 letters in TN eyes and +0.1/-3.4 letters in PT eyes (p < 0.001/p < 0.001). The percentage of ≥15 letters gainers/losers at 24 months was 24.8%/14.5% in TN, and 10.3%/15.7% in PT eyes. The median number of injections/visits at 12 months was 7/9 in TN and 6/8 in PT (p=0.002/p < 0.001) and at 24 months was 11/16 in TN and 11/14 in PT (p=0.329/p < 0.001). Study drugs included ranibizumab (39.5%), aflibercept (41.2%) and bevacizumab (19.3%). Independent, large-scale national audits are feasible if committed health care professionals are provided with efficient information technology systems to do them. The results described here represent an adequate measurement of the quality of care delivered nationwide and benchmark the clinical management of nAMD at a country level compared to other real-world international cohorts.

Additive Value of a Face-to-Face Visit to Virtual Remote Decision in Patients with Neovascular Age-Related Macular Degeneration

Introduction: The increasing high prevalence of neovascular age-related macular degeneration (nvAMD) in the aging population combined with the need for frequent monitoring and treatment for many years, especially in the COVID-19 era, raises the need to establish an effective, reliable, and safe follow-up and treatment model. This study evaluates the difference in treatment decisions comparing between the gold standard face-to-face clinical examination and virtual evaluation approach based only on visual acuity (VA) and optical coherence tomography (OCT) scans without clinical fundoscopic examination in nvAMD patients. Methods: A single-center retrospective cohort study was conducted that compared an original “face-to-face” visit treatment decision regarding the need for anti-vascular endothelial growth factor drug, interval, and treatment regimen based on routine VA, spectral domain OCT imaging, and dilated fundus examination to two “virtual” treatment decisions based on evaluation of OCT scans and previous medical records before and after revealing VA data on the same nvAMD patients eyes. Results: About 169 eyes of 114 patients were included in the study. Forty-nine patients (43%) suffered from bilateral nvAMD and had both eyes included in the study. Agreement between the “face-to-face visit treatment decision” and “virtual treatment decision” was noted in 74.6% and 71.6% eyes before and after revealing the patient’s VA in the study visit, respectively. Conclusions: Virtual evaluation results in similar treatment decisions for nvAMD patients compared to standard face-to-face clinical examination.

When to Perform a Treatment Switch in Diabetic Macular Edema in Patients with Inadequate Response to Anti-VEGF

Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Multiple therapeutic options are currently available for these patients, including laser photocoagulation; intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs or steroids; or pars plana vitrectomy for tractional DME. The initial treatment for DME is well-defined and widely accepted, with anti-VEGF as first-line option. Nevertheless, between 30 and 40% of patients show partial response or no response whatsoever. There is no consensus on the number of injections needed in order to classify a patient as a non-responder or sub-optimal responder, nor on the definition of the latter. In this study, these concepts are analysed as well as the different therapeutic alternatives at hand, with special interest on the switch between different anti-VEGF and/or steroids. These analyses are performed from an anatomical and functional point of view as well as from an economic, cost-effectiveness perspective. Recent evidence suggests that an early switch to dexamethasone implant in eyes that did not respond adequately to anti-VEGF therapy after 3 injections provides better functional outcomes while alleviating the heavy economic burden of this disease.

Towards the Development of Longer and More Efficacious Therapies for Wet and Dry Age-related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of vision loss in developed countries. The advanced stages of AMD are characterized by the onset and progression of macular neovascularization or geographic atrophy. Several treatments are currently available for managing the neovascular form of AMD, based on intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs. Although these agents are efficient in inducing fluid regression and preserving visual function, their limited duration of action and treatment burden are stimulating the development of new molecules with more prolonged pharmacological activity. The future of exudative AMD therapies will include new generations of anti-VEGF drugs, surgical anti-VEGF port delivery systems and novel molecules acting on other AMD pathogenic pathways. In contrast, dry AMD and geographic atrophy have no approved treatments; nutraceutical approaches still represent the only way to reduce the probability of AMD progression and the onset of complications. Several ongoing clinical trials are testing different molecules that have been developed to slow the progression of geographic atrophy, including complement system inhibitors, integrin inhibitors, gene therapies and cell-based therapies. In this review, we provide an overview of the current state of the art and future perspectives for the management of dry and wet AMD.

Novel Dual-Targeting Antibody Fragment IDB0062 Overcomes Anti-Vascular Endothelial Growth Factor Drug Limitations in Age-Related Macular Degeneration.

PurposeRepeated administration of anti–vascular endothelial growth factor drugs to treat age-related macular degeneration leads to resistance. To overcome this drawback, we developed the novel recombinant dual-targeting antibody fragment IDB0062, which is comprised of the anti–vascular endothelial growth factor A Fab and neuropilin 1-targeting peptide, and we assessed its properties.MethodsWe compared the in vitro activity of IDB0062 and conventional drugs using cell proliferation, wound healing, and Transwell assays. The in vivo efficacy of IDB0062 was determined using mouse choroidal neovascularization and oxygen-induced retinopathy models. To evaluate the ocular distribution of IDB0062, we intravitreally administered IDB0062 and ranibizumab to cynomolgus monkeys and measured the retinal drug levels.ResultsIDB0062 effectively inhibited not only vascular endothelial growth factor A in vitro but also placenta growth factor 2, vascular endothelial growth factor B, and platelet-derived growth factor BB, which induce vascular endothelial growth factor A–independent angiogenesis. In addition, IDB0062 showed non-inferior efficacy compared with aflibercept in vivo despite the low selectivity for mouse vascular endothelial growth factor A. In the monkey intravitreal pharmacokinetic study, IDB0062 improved drug distribution in the retina compared with ranibizumab, confirming the accelerated onset of pharmacological action when IDB0062 is injected in the vitreous humor.ConclusionsThrough neuropilin 1 binding, IDB0062 can improve the efficacy and accelerate the onset of pharmacological action in the posterior segment, which is targeted for macular degeneration, thereby improving drug responsiveness in drug-resistant patients.Translational RelevanceConsidering its novel mechanism of action, IDB0062 may help in controlling resistance to conventional anti–vascular endothelial growth factor drugs in clinical settings.

Three-Year Outcomes of Wet Age-Related Macular Degeneration Treatment in Polish Therapeutic Programs.

Background and Objectives: Wet age-related macular degeneration (wAMD) is a chronic, progressive disease of the central part of the retina. Standard treatment for wAMD consists of multiple intravitreal injections of anti-vascular endothelial growth factor drugs. The study goal was to evaluate the three-year effectiveness of wAMD treatment with aflibercept and ranibizumab as part of the therapeutic program in routine clinical practice. Materials and Methods: 1430 patients (possessing 1430 wAMD eyes) with median age of 78.0 years (71.0, 83.0) were enrolled in a non-randomized, retrospective, observational, multicenter study; 804 (56.2%) eyes were treatment-naïve. Therapy was carried out in accordance with the guidelines of the treatment program (the fixed or pro re nata regimen). Results: After the first year of treatment, there was a gain of 2.03 (12.15) letters; after the second, 0.94 (13.72) (p ˂ 0.001); and after the third, 0.17 (14.05) (p ˂ 0.001). There was a significant reduction in the central retinal thickness. In the first year, the patients received 7.00 (5.00, 8.00) injections. In the following years, a significantly lower number of injections (4.00 (2.00, 5.00)) was administered. After the first year, there was a significant difference in the distribution of the best corrected visual acuity according to the Early Treatment Diabetic Retinopathy Study protocol, with more frequent values in the ranges > 35 ≤ 70 for this parameter and > 70 letters in the treatment naïve eye subgroup. After the first year, central retinal thickness in treatment-naïve eyes was significantly reduced. Conclusions: Regular treatment of wet age-related macular degeneration as part of the treatment program achieves functional stabilization and significant morphological improvement over a long-term, three-year follow-up, with significantly fewer injections needed after the first year of treatment.

Nanotechnology for Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.

Retinal arterial macroaneurysm in a patient with arterial hypertension

Purpose: To present a case of retinal arterial macroaneurysm in a 48–year–old male patient with systemic arterial hypertension.&#x0D; Case report: A 48–year–old male was admitted to our department because of progressive deterioration of visual acuity in his right eye. He reported diplopia and blurred central field vision. The patient was treated for systemic arterial hypertension and had no other known medical problems. Medical treatment, examination results, and therapy were presented in this case report.&#x0D; Conclusions: In the treatment of patients with retinal arterial macroaneurysm a holistic approach is important. In an attempt to optimize the final outcome of the patient's treatment, both the ocular symptoms and systemic risk factors should be treated. Therapeutic interventions for eyes with retinal arterial macroaneurysm include laser photocoagulation, pneumatic displacement of haemorrhage, vitreoretinal surgical techniques, the use of neodymium–doped yttrium aluminium garnet or argon laser, and intravitreal injections of anti–vascular endothelial growth factor drugs. Their precise roles should be evaluated in further studies.

Retinal Diseases Regulated by Hypoxia-Basic and Clinical Perspectives: A Comprehensive Review.

In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.

Genetic Polymorphisms Affecting Ranibizumab Response in High Myopia Patients.

High myopia is an ophthalmic pathology that affects half of the young adults in the United States and Europe and it is predicted that a third of the world’s population could be nearsighted at the end of this decade. It is characterized by at least 6 diopters or axial length > 26 mm and, choroidal neovascularization (CNV) in 5 to 11% of cases. Ranibizumab is a recombinant humanized monoclonal antibody fragment. It is an anti-vascular endothelial growth factor (anti-VEGF) drug used in the treatment of CNV. Many genetic polymorphisms have been associated with interindividual differences in the response to ranibizumab, but these associations were not yet assessed among patients with high myopia and CNV. We performed a retrospective study assessing the association of genetic polymorphisms with response to ranibizumab in patients with CNV secondary to high myopia (mCNV). We included genetic polymorphisms previously associated with the response to drugs used in CNV patients (bevacizumab, ranibizumab, aflibercept, and photodynamic therapy (PDT)). We also included genetic variants in the VEGFA gene. Based on our results, ARMS2 (rs10490924) and CFH (rs1061170) are associated with response to ranibizumab in high myopia patients; and, included VEGFA genetic polymorphisms are not associated with ranibizumab response in our population but might be related to a higher risk of CNV.

A comparative study of three intraoperative real-time fundus examinations in cataractous eyes

Objective: To investigate whether the wide field imaging system (WFIS), 25G optical fiber and intraoperative optical coherence tomography (iOCT) can perform real-time screening and diagnosing in patients with highly suspected fundus diseasesintraoperatively. Methods: A cross-sectional study was carried out. One hundred and eighty-three densely cataractous eyes of 183 patients with suspected fundus diseases were included in the Affiliated Hospital of Nantong University from July 2019 to June 2020. Lens phacoemulsification combined with intraocular lens implantation was performed in these eyes. Following the opaque lens was removed, the patients were divided into 4 groups according to fundus examination methods: WFIS SW-8000 group (49 eyes), 25G optical fiber group (40 eyes), iOCT group (36 eyes), and combination group of three examination methods (58 eyes). Optical coherence tomography and/or fundus fluorescence angiography were used to detect the fundus after surgery. The intraoperative and postoperative examination results were compared to verify the accuracy of intraoperative diagnosis in each group. Chi-square test was used for statistical analysis. Results: There were 79 males and 104 females in all patients, and the mean age was (69±10) years. Intraoperative examinations showed 82 eyes with fundus disease (positive rate was 44.81%), while postoperative examinations revealed 93 eyes with fundus disease (positive rate was 50.82%). In the WFIS SW-8000 group, fundus disease was found in 19 eyes intraoperatively and 26 eyes postoperatively (sensitive rate was 73.08%). In the 25G optical fiber group, fundus disease was found in 18 eyes intraoperatively and 20 eyes postoperatively (sensitive rate was 90.00%). In the iOCT group, fundus disease was observed in 20 eyes administratively and 22 eyes postoperatively (sensitive rate was 90.91%). In the combination group, fundus disease was observed in 25 eyes intraoperatively, which was consistent with the results of postoperative examinations (sensitive rate was 100.00%). There were statistically significant differences in the diagnostic sensitivity of fundus diseases among different methods (χ²=9.26; P<0.05). The diagnostic sensitivity of fundus diseases of the WFIS SW-8000 group was lower than that of the the combination group, the difference was statistically significant (χ²=7.80, P<0.01), and there was no significant difference between the other two groups (all P>0.05). Forty-nine eyes with fundus neovascular disease or severe macular edema requiring drug intervention were identified intraoperatively, and intravitreal anti-inflammatory and/or anti-vascular endothelial growth factor drugs were injected in 41 eyes. Conclusions: The WFIS, 25G optical fiber and iOCT can be used to examine the fundus and detect fundus disease intraoperatively, facilitating timely diagnosis and treatment of retinopathy in patients with dense cataract. The combined application of the three methods has the highest sensitivity. (Chin J Ophthalmol, 2021, 57: 850-856).

Effects of Anti-Vascular Endothelial Growth Factor Drugs Before and After Pars Plana Vitrectomy in Patients with Polypoidal Choroidal Vasculopathy and Vitreous Hemorrhage.

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.

Conbercept for Treatment of Neovascular Age-Related Macular Degeneration and Visual Impairment due to Diabetic Macular Edema or Pathologic Myopia Choroidal Neovascularization: A Systematic Review and Meta-Analysis.

Background: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug. Here, we systematically conducted the efficacy, safety, compliance, and pharmacoeconomic evaluation of intravitreal conbercept (IVC) compared with other treatments in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or pathologic myopia choroidal neovascularization (pmCNV). Methods: Databases of PubMed, Embase, Cochrane Library, ClinicalTrials.gov, SinoMed, China National Knowledge Infrastructure, and WanFang Data were systematically searched from the inception to July 27, 2021. Randomized clinical trials and pharmacoeconomic studies comparing IVC with control groups in adults with nAMD, DME, or pmCNV were reviewed and selected. Meta-analyses were performed using the fixed-effects model when pooled data were homogeneous. Heterogeneous data were analyzed using the random-effects model. Primary outcomes included visual improvement rate, mean change in visual acuity or best corrected visual acuity, and pharmacoeconomic outcomes. Additional outcomes were the mean change in fundus examination values, adverse events (AEs), quality-of-life measures, and number of injections. Results: Among 3,591 screened articles, 22 original studies with 1,910 eyes of patients were finally included. For nAMD and DME, IVC was significantly associated with better visual acuity or best corrected visual acuity improvement and fundus quantitative measures than placebo, laser photocoagulation (LP), or intravitreal triamcinolone acetonide (IVT). However, IVC showed non-inferior efficacy to intravitreal ranibizumab (IVR) according to low quality of evidence, and there was lack of trials comparing the priority of IVC to other anti-VEGF regimens. No definitive increased risk of ocular or non-ocular AEs were observed in the study groups. All patients with AEs recovered after symptomatic treatments, and no severe AEs occurred. Patients treated with IVC might have higher quality-of-life scores than those in IVR in nAMD or LP in DME. Additionally, IVC showed cost–utility advantages in nAMD and cost-effectiveness advantages than IVR in pmCNV in China. Conclusion: IVC is well-tolerated and effective for improving vision acuity and quantitative measures in fundus condition in patients with nAMD and DME compared with LP, IVT, and placebo, but gains comparable efficacy to IVR. However, well-designed, large-sample, and long-term evaluation of IVC shall be conducted in additional studies worldwide.

Effects of Intravitreal Injection of Anti-vascular Endothelial Growth Factor Drugs on Ocular Blood Vessels and Blood Flow in Patients with Diabetic Retinopathy

Diabetic retinopathy(DR)is the major microvascular disease in diabetic patients,and it is also one of the main blinding eye diseases in the current population.The typical pathological change of DR in the eyes is vascular endothelial growth factor(VEGF)-mediated neovascularization induced by retinal ischemic stimulation.Therefore,anti-VEGF drugs have gradually become one of the mainstream methods to treat DR and DR-induced diseases such as diabetic macular edema.Recent studies have proved that anti-VEGF drugs have certain effects on ocular blood vessels and blood flow in patients with DR,while the specific mechanism has not been fully elucidated.This article summarizes the research progress on the effects of intravitreal injection of anti-VEGF drugs on the ocular blood vessels and blood flow in patients with DR.

Addition of photodynamic therapy to anti-vascular endothelial growth factor drugs compared to anti-vascular endothelial growth factor monotherapy for polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy is characterized by multiple and recurrent serosanguineous detachments of the retinal pigment epithelium and aneurysmal protrusions in the choroidal vessels. Different therapeutic options have been proposed, including anti-vascular endothelial growth factor drugs and photodynamic therapy. Controversy exists as to whether combination therapy is superior to anti-vascular endothelial factor drugs alone. We searched Epistemonikos, the largest database of systematic reviews in health, maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane. We extracted data from the identified reviews, analyzed the data from the primary studies, performed a meta-analysis, and prepared a summary table of the results using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. We identified three systematic reviews that together included twelve primary studies. Of these, two were randomized trials, and only one of them was included in the analysis. The addition of photodynamic therapy may result in little or no difference in the incidence of retinal hemorrhage and visual acuity gain at six months (low certainty of evidence). On the other hand, the combination of photodynamic therapy and anti-vascular endothelial growth factor drugs compared to anti-vascular endothelial growth factor alone is likely to increase polyp regression at three and six months and reduce central retinal thickness at six months.

Efficacy and safety of single-dose dexamethasone implantation for patients with persistent diabetic macular edema: a systematic review and meta-analysis.

This meta-analysis was conducted to evaluate the efficacy and safety of single-dose dexamethasone implantation for treating persistent DME (diabetic macular edema) refractory to anti-VEGF (anti-vascular endothelial growth factor) drugs over a period of 6months. All related clinical trials were reviewed by searching electronic databases of PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. The primary outcome parameters were best-corrected visual acuity (BCVA) and central macular thickness (CMT). We performed this meta-analysis by using Stata15.0. Ten clinical trials involving 362 eyes from 328 patients were eligible in the final analysis. After single-dose dexamethasone implantation, there was a significant improvement in BCVA from baseline to 1, 3, and 6months with an average increase of - 0.15 logMAR (p < 0.001), - 0.14 logMAR (p < 0.001), and - 0.07 logMAR (p = 0.004), respectively. Further, mean CMT decreased significantly with an average reduction of 249.18μm (p < 0.001), 217.66μm (p < 0.001), and 91.56μm (p < 0.001) at months 1, 3, and 6, respectively. Our results indicate that switching to a dexamethasone implant could achieve significant anatomical and functional improvement among patients with refractory DME. Clinicians should be aware of this treatment option in refractory DME.

Treatment of Neovascular Age-Related Macular Degeneration: An Economic Cost-Risk Analysis of Anti–Vascular Endothelial Growth Factor Agents

To find the best cost-effective neovascular age-related macular degeneration (nAMD) treatment to improve vision while avoiding complications. The model is based on a cost-risk tradeoff analysis from policymakers' perspective. A powerful and flexible simulation modeled outcomes of 2 years of treatment with the 4 commonly used anti-vascular endothelial growth factor drugs (bevacizumab, ranibizumab, aflibercept, and brolucizumab) across 3 injection protocols, building on prior findings that these drugs are noninferior. The model incorporates blinding complications, their management, and associated costs to society. Each option and several what-if scenarios were simulated 1,000 times with 100,000 hypothetical patients. One hundred thousand simulated patients using data from published clinical trials. Case- and eye-specific cost-risk economic analysis. Costs of nAMD treatment per patient and number of eyes that become blind as a result of treatment over 2 years. Using published prices and fees, the injection protocol that follows published clinical studies, results showed that the mean±standard deviation cost per patient were $16,859 ± $3.65, $32,949 ± $3.27, $39,831 ± $3.80, and $53,056 ± $2.99 for bevacizumab, brolucizumab, aflibercept, and ranibizumab, respectively. The numbers±standard deviations of treated eyes that became blind were 108 ± 10.18, 694 ± 26.66, 168 ± 12.83, and 108 ± 10.52, respectively. We further provide a lower bound (when all patients are maximally extended) and upper bound (when no patient is extended) to these numbers. For brolucizumab, the upper bound is the 2-month interval injection protocol. Taking a policymaking perspective, this study suggested that bevacizumab is the preferred first-line therapy. Recommendation for second-line therapy depends on the extent of the policymaker's risk aversion because of the tradeoff between cost and risk of blindness as a result of treatment. If risk neutral, the least expensive option (brolucizumab) is preferred. But if policymakers are moderately to highly risk averse, then aflibercept or ranibizumab are preferred. Because medical advances and different costs may change our findings, we provide a free application (https://eye-inj.shinyapps.io/calc/) for readers who wish to use different cost structures. Simulating outcomes is an innovative approach, unique in ophthalmology, and presents a significant opportunity because it can be adapted easily to different settings (using different costs, risks, and protocols) and to other diseases (e.g., diabetic macular edema), to ultimately improve wide-scale decision-making and use of funds.

Therapy of Age-related Exudative Macular Degeneration with Anti-vascular Endothelial Growth Factor Drugs: An Italian Real Life Study

Aim: To evaluate the real utilization of ranibizumab and aflibercept in the daily management of patients with neovascular age-related macular degeneration (nAMD) treated at the Eye Clinic of Campania University L.Vanvitelli. Background: Therapy with anti-vascular endothelial growth factor represents the gold standard in wet age-related macular degeneration. There are nonreal life italian studies of this therapy in the literature. Objective: To analyze in our sample the post-therapy variations of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) observed at the end of a 12-month follow-up period. Methods: This real-life study analyzes 109 patients that underwent monthly checks for the first 4 months and then every 2 months until the end of the 12-month follow-up. The sample was first analyzed in its entirety, subsequently subdivided into 3 groups based on baseline BCVA, age, and the number of intravitreal injections performed, in order to identify possible predictive elements of the anti-VEGF response. Results: On average, patients underwent 4.16 ± 1.58 intravitreal anti-VEGF injections in 1 year. At the end of the 12-month follow-up, the patients’ average BCVA increased from 33.01 letters to 33.75 letters (+0.74 ± 9,4 letters), while the average CRT decreased from 346.86 µm to 265.39 µm (-81.47 ± 121 µm). Conclusion: The study shows the efficacy of anti-VEGF therapy in the stabilization of BCVA in nAMD, confirming the differences in visual outcomes compared to clinical trials, mainly for economic-organizational reasons.