Anti-vascular Endothelial Growth Factor Drugs Research Articles

Clinical Effect of Tongmai Fuming Decoction on Neovascular Ophthalmopathy.

Background The incidence of neovascular eye disease is increasing year by year, seriously threatening human vision health and becoming an urgent public health problem. Tongmai fuming decoction as an experienced prescription can treat ischemic eye disease. Objective To investigate the therapeutic effect of Tongmai fuming decoction combined with anti-VEGF therapy on neovascular ophthalmopathy. Methods 52 patients (62 eyes) with neovascular ophthalmopathy who met the inclusion criteria from January 2018 to July 2020 were randomly divided into the control and observation groups. The control group was given an intravitreal injection of antivascular endothelial growth factor (VEGF) drugs once a day combined with on-demand treatment. The observation group was treated with traditional Chinese medicine Tongmai fuming decoction in addition to the treatment of anti-VEGF drugs. The best-corrected visual acuity (BCVA) was examined before and after treatment, and optical coherence tomography angiography (OCTA) was used to examine the mean retinal thickness and neovascularization in the macular area. Patients were followed for one year and the number of anti-VEGF injections was recorded. Results After treatment, the average thickness of BCVA and macular retina in the two groups significantly improved. The BCVA of the control group was 0.59 ± 0.39 3 months after treatment, and that of the experimental group was 0.42 ± 0.25 3 months after treatment. The average thickness of the macular retina in the control group was 304.8 ± 79.7 3 months after treatment, and that in the experimental group was 267.7 ± 64.6 3 months after treatment; The average number of injections of anti-VEGF therapy in the control group was 2.32 ± 1.15 times, and that in the experimental group was 1.74 ± 0.76 times. There was a significant difference between the two groups. Conclusion Tongmai fuming decoction and anti-VEGF therapy have a synergistic effect in the treatment of neovascular ophthalmopathy, which can reduce the treatment times of anti-VEGF drugs.

Evaluation of off-label anti-vascular endothelial growth factor and steroid implant medication uses in macular edema due to retinal vein occlusion in Turkey.

Retinal vein occlusion (RVO) is one of the most common causes of vision loss. Anti-vascular endothelial growth factor (anti-VEGF) drugs, ranibizumab and aflibercept, and corticosteroid implants are approved treatment options for RVO-related macular edema (ME) in Turkey. To the best of our knowledge, there is no data regarding the off-label use of these drugs for RVO in English literature. We aimed to evaluate the clinical and demographic characteristics of off-label drug use applications in Turkey for RVO. Applications made to the Turkish Medicines and Medical Devices Agency between January 1 and December 31, 2018, for the use of off-label drugs (ranibizumab, aflibercept, dexamethasone implant) for the diagnosis of RVO from hospitals across Turkey were retrospectively analysed. Data of the applications, such as demographic characteristics, previous treatment regimens, reasons for applications, applicant hospitals and their regions, were recorded. There were 291 approved applications for RVO. The mean age of the patients was 64.88 ± 10.78 years, 48.8% were male, and 51.2% were female. Of these applications, 44.7% were for aflibercept, 35.7% for ranibizumab and 19.6% for dexamethasone implant. No application was made for bevacizumab since it could be used without needing for an application. The most common reasons for applications were due to dose limitations, failure to complete loading doses, and glaucoma, respectively. In terms of the distribution of the applicant hospitals, public university hospitals ranked first with 72.5%, training and research hospitals ranked second with 14.7% and foundation university hospitals ranked third with 13.1% rates. The practice of drug use in RVO in Turkey has changed as of the beginning of 2019. Stepwise therapy has been accepted by the drug regulatory agency Turkish Medicines and Medical Devices Agency. Utilization of licensed drugs, aflibercept, ranibizumab and dexamethasone has been allowed only after administration of 3 doses of intravitreal bevacizumab. After 3 doses of bevacizumab, the physician may continue either with bevacizumab again or a dexamethasone implant. If there is a reason such as the presence of glaucoma, the physician may skip dexamethasone and switch to aflibercept and ranibizumab, but in this case, dexamethasone cannot be administered to the patient for life. The evaluation of the off-label treatments of RVO, which is one of the most frequently followed diseases in retina clinics, not only contributes to the literature but also provides information regarding the most frequently applied treatments and the physicians' off-label drug preferences for RVO.

Glycemic Control after Initiation of Anti-VEGF Treatment for Diabetic Macular Edema.

Diabetic macular edema (DME) induces visual disturbance, and intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs are the accepted first-line treatment. We investigate its impact on glycemic control after starting VEGF treatment for DME on the basis of a questionnaire and changes in hemoglobin A1c (HbA1c). We conducted a retrospective multicenter study analyzing 112 patients with DME who underwent anti-VEGF therapy and their changes in HbA1c over two years. Central retinal thickness and visual acuity significantly improved at three months and throughout the period after initiating therapy (p < 0.0001); a significant change in HbA1c was not found. A total of 59.8% of patients became more active in glycemic control through exercise and diet therapy after initiating therapy, resulting in a significantly lower HbA1c at 6 (p = 0.0047), 12 (p = 0.0003), and 18 (p = 0.0117) months compared to patients who did not. HbA1c was significantly lower after 18 months in patients who stated that anti-VEGF drugs were expensive (p = 0.0354). The initiation of anti-VEGF therapy for DME affects HbA1c levels in relation to more aggressive glycemic control.

Efficacy and mechanism of anti-vascular endothelial growth factor drugs for diabetic macular edema patients

BACKGROUNDDiabetes is a serious public health concern in China, with 30% of patients developing retinopathy, and diabetic macular edema (DME) having the biggest impact on vision. High blood glucose level can cause retinal cell hypoxia, thus promoting vascular endothelial growth factor (VEGF) formation and increasing vascular permeability, which induces DME. Moreover, cell hypoxia can accelerate the rate of apoptosis, which leads to the aging of patients. In severe cases, optic cell apoptosis or retinal fibrosis and permanent blindness may occur.AIMTo investigate and compare the efficacy, mechanism, and differences between two anti-VEGF drugs (Compaq and ranibizumab) in DME patients.METHODSNinety-six patients with DME who attended our hospital from April 2018 to February 2020 were included and randomly divided into two groups (Compaq group and ranibizumab group). The groups received vitreal cavity injections of 0.5 mg Compaq and 0.5 mg ranibizumab, respectively, once a month. The best corrected visual acuity (BCVA), intraocular pressure (IOP), macular retinal thickness (CMT), macular choroidal thickness (SFCT), foveal no perfusion area (FAZ), superficial capillary density, deep capillary density, treatment effect, and adverse reactions were compared before and after treatment and between the two groups.RESULTSBefore treatment and 1-mo post-treatment, there was no statistically significant difference in the estimated BCVA in both groups (P > 0.05). BCVA decreased in the Compaq group 3 mo after treatment, and the difference was statistically significant (P < 0.05). Before treatment, and 1 mo and 3 mo post-treatment, there was no statistically significant difference in the estimated IOP in either group (P > 0.05). Before treatment and 1-mo post-treatment, there was no statistically significant difference in the estimated CMT, SFCT, or FAZ in either group (P > 0.05). CMT and SFCT values decreased in the Compaq group 3 mo post-treatment, and the difference was statistically significant (P < 0.05). Before treatment, and 1 mo and 3 mo post-treatment, there were no statistically significant differences in vascular density in the shallow or deep capillary plexi of the fovea, parafovea, or overall macular area between the two groups (P > 0.05). Marked efficient, effective, and invalid rates were 70.83% and 52.08%, 27.08% and 39.58%, and 2.08% and 8.33% in the Compaq and ranibizumab groups, respectively. The differences between the two groups were statistically significant (P < 0.05).CONCLUSIONAnti-VEGF drugs can effectively improve CMT and SFCT, without affecting microcirculation, thus providing an effective and safe treatment for patients with DME.

Metabolic Symbiosis-Blocking Nano-Combination for Tumor Vascular Normalization Treatment.

The clinical anti-vascular endothelial growth factor (anti-VEGF) drugs and metronomic chemotherapy (MET) induced tumor vascular normalization treatment (TVNT) are easily antagonized by tumor microenvironment metabolic cross-talk between tumor cells and endothelial cells (ECs). To overcome this dilemma, nanodrug with the ability of ECs targeted glycolysis inhibition and nanodrug with the ability of tumor cell glycolysis inhibition, anti-VEGF, and MET are combined to prepare Nano-combination the pathways related to angiogenesis, tumor cell proliferation, and immunosuppression and breaking the negative sugar-lipid-protein metabolism balance in tumor microenvironment. Thus, stronger and more lasting normalized tumor vascular network and remarkable antitumor efficacy are obtained after treatment, constructing a positive feedback loop between TVNT and anti-tumor therapy. Above all, this study provides a new insight for solving the bottleneck of clinical TVNT.

Changes in Scleral Thickness Following Repeated Anti-vascular Endothelial Growth Factor Injections.

PurposeThis cross-sectional study aimed to compare changes in scleral thickness between eyes injected with repeated anti-vascular endothelial growth factor (anti-VEGF) drugs and fellow injection naive eyes using optical coherence tomography (OCT).MethodsA total of 79 patients treated with three intravitreal anti-VEGF injections in one eye versus no injections in the fellow eye were included.Anterior segment-OCT measured scleral thickness in the inferotemporal quadrant 4 mm away from the limbus.Results Injected eyes had a mean scleral thickness of 588 95 μm versus 618 85 μm in fellow naïve eyes (P 0.001). Comparing injected eyes to fellow naïve eyes stratified by injection number showed a mean scleral thickness of 585 93 μm versus 615 83 μm in eyes with 3–10 injections (n = 32, P = 0.042); 606 90 μm versus 636 79 μm in eyes with 11–20 injections (n = 24, P = 0.017); and 573 104 μm versus 604 93 μm in eyes with 20 injections (n = 23, P = 0.041). There was no significant correlation between injection number and scleral thickness change (r = –0.07, P = 0.26). When stratified by indication, subjects with retinal vein occlusions showed a statistically significant difference in scleral thickness between injected and fellow naïve eyes (535 94 μm and 598 101 μm, respectively, P = 0.001).ConclusionCompared to injection naive eyes,multiple intravitreal injections at the repeated scleral quadrant results in scleral thinning. Consideration of multiple injection sites should be considered to avoid these changes.

A systematic review of clinical practice guidelines for myopic macular degeneration.

BackgroundMyopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization.MethodsA systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict.ResultsAfter applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty.ConclusionsThe outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.

Anatomical and functional responses to single brolucizumab injection in neovascular age-related macular degeneration patients not responding to antiangiogenics: a case series

Introduction: Neovascular age-related macular degeneration (nAMD) is treated with antivascular endothelial growth factor (anti-VEGF) drugs. However, resistance to anti-VEGF therapy is observed in some patients. Brolucizumab is a new-generation anti-VEGF drug for the treatment of nAMD, with proven efficacy in fluid resolution and long-lasting effects. Methods: We report here a case series of nAMD patients not responding to previous anti-VEGF therapy showing anatomical and functional response to a single intravitreal injection of brolucizumab. Results: Nine patients with nAMD, undergoing treatment with anti-VEGF therapy (aflibercept, bevacizumab, or ranibizumab) but with either fluid persistence or frequent fluid recurrences in retinal compartments, were switched to intravitreal brolucizumab and examined 4 weeks postinjection. No signs of active disease were observed in all but one patient, with complete retinal fluid resolution in seven patients. Central macular thickness and visual acuity significantly improved, and changes were sustained for up to 12 weeks in a subset of three patients. No adverse reactions were observed. Conclusions: This new anti-VEGF drug showed great efficacy since the first week from the injection with a significative reduction of subretinal fluid and rapid improvement of visual acuity. In conclusion, brolucizumab administered intravitreally appears to be an effective treatment in nAMD patients, leading to both early anatomical and functional improvements.

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.