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1.
Vestn Oftalmol ; 137(1): 83-93, 2021.
Artigo em Russo | MEDLINE | ID: mdl-33610155

RESUMO

The problem associated with the prevalence of retinal diseases, and age-related macular degeneration (AMD) in particular, is undoubtedly relevant. This aspect is based on steadily growing statistics on morbidity, a high number of randomized controlled trials (RCT) and published real world data (RWD). The analysis of RCT results being published by researchers on 15.05.19 showed 2915 studies were registered on the subject of retinal diseases; that exceeds the number of studies on glaucoma by approximately 1.38 times (2118 studies) and conjunctival lesions by 2.37 times (1230 studies). AMD is one of the leading causes of irreversible vision loss and blindness; its neovascular form leads to blindness in 80-90% of all cases. Even though the topic of nAMD therapy is widely highlighted in modern ophthalmology, today there are many aspects that require targeted solutions. The main controversial issues that determine the complexity of therapy and patient management include discrepancies in determination of reference points (disease activity criteria) for implementation of anti-VEGF dosing regimens, patients' compliance, prioritization issues in treatment, its continuity with potential for the increase of intervals between injections and monitoring visits.


Assuntos
Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico
2.
J Fr Ophtalmol ; 44(3): 299-306, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33608176

RESUMO

OBJECTIVES: To investigate the effects of the COVID-19 pandemic on the treatment course of neovascular age-related macular degeneration (nAMD) patients who received anti-VEGF injection therapy with real-life data. METHODS: This retrospective study consisted of 116 eyes of 106 patients. Ophthalmic examination, assessment of best-corrected visual acuity (BCVA), optical coherence tomography (OCT) findings and data of last two visits before restrictions (V-2 and V-1) and the first visit (V0) after the release of national lockdown and subsequent visits (V1 and Vlast) were recorded. The lockdown period was determined by the time interval between March 11 and June 1, 2020. MAIN RESULTS: The injection interval before V-1 was significantly longer than the interval after V0 (2.56±0.9 vs. 2.14±0.8 months, P=0.02). While the median central macular thickness (CMT) was significantly increased at V0 compared to V-1 [274(132-711) vs. 238(136-628), P<0.001], the median CMT was significantly lower at V1 compared to V0 [256 (136-591) vs. 274(132-711), P=0.003]. The median BCVA was 0.67(0.1-1.1) logMAR at V-1 and significantly worsened to 0.78 (0.1-1.2) logMAR at V0 (P=0.003). Although the median BCVA improved to 0.69 logMAR (0.1-1.2) at Vlast, the difference did not reach statistical significance compared to V0 (P=0.08). CONCLUSION: Treatment delay due to the COVID-19 pandemic cause progression of nAMD and visual impairment. To plan more frequent anti-VEGF treatments and visits may be an appropriate approach until the disease stabilizes. However, it should be kept in mind that despite the improvement in OCT findings, the desired success in VA could not be achieved in the short term.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular , Pandemias , Neovascularização Retiniana , Tempo para o Tratamento , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Diagnóstico Tardio/estatística & dados numéricos , Progressão da Doença , Feminino , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Degeneração Macular/patologia , Masculino , Pandemias/estatística & dados numéricos , Exame Físico/estatística & dados numéricos , Prognóstico , Neovascularização Retiniana/diagnóstico , Neovascularização Retiniana/tratamento farmacológico , Neovascularização Retiniana/epidemiologia , Neovascularização Retiniana/patologia , Estudos Retrospectivos , Tempo para o Tratamento/estatística & dados numéricos , Tomografia de Coerência Óptica , Resultado do Tratamento , Turquia/epidemiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
3.
Biomed Pharmacother ; 133: 111041, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378949

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1)-dependent cell death in the retinal pigment epithelium (RPE) is implicated in dry age-related macular degeneration (AMD). Although PARP1 inhibitors are available for treating dry AMD, their delivery route is not ideal for patients. The aim of this study was to test the efficacy of a novel PARP1-inhibitory compound (PIC) in vitro and in vivo. This study presents PIC, a novel small molecule, with superior efficacy to PARP1 inhibitors in the market. PIC demonstrated a distinctive inhibitory profile against PARP isotypes than the FDA-approved PARP1 inhibitors. PIC inhibited PARP1 activation at an IC50 of 0.41 ± 0.15 nM in an enzyme-based assay in vitro and at IC50 and EC50 in ARPE-19 cells of 0.11 ± 0.02 nM and 0.22 ± 0.02 nM, respectively, upon H2O2 insult. PIC also moderated mitochondrial fission and depolarization and maintained cellular energy levels under oxidative stress in ARPE-19 cells. Furthermore, PIC demonstrated good corneal penetration in a rat model, presenting PIC as a promising candidate for eye drop therapeutics for dry AMD. When PIC was administered as an eye drop formulation, RPE morphology was preserved, maintaining the thickness of the outer nuclear layers under sodium iodate (SI) treatment in rats. In SI-treated rabbits, eye drop administration of PIC also retained the structural and functional integrity when analyzed using funduscopy and electroretinogram. Collectively, our data portray PIC as an attractive treatment measure for dry AMD.


Assuntos
Degeneração Macular/tratamento farmacológico , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Administração Oftálmica , Animais , Antioxidantes/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Humanos , Iodatos , Degeneração Macular/induzido quimicamente , Degeneração Macular/enzimologia , Degeneração Macular/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Absorção Ocular , Soluções Oftálmicas , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Coelhos , Ratos Sprague-Dawley , Epitélio Pigmentado da Retina/enzimologia , Epitélio Pigmentado da Retina/patologia
4.
Vestn Oftalmol ; 136(6. Vyp. 2): 227-234, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33371654

RESUMO

Age-related macular degeneration is an advanced chronic disease and the main cause of vision loss in geriatric patients. Optical coherence tomography (OCT) is a modern method of retinal imaging allowing to detect different types of fluid: intraretinal fluid (IRF), subretinal fluid (SRF) and fluid under pigment epithelial detachment (PED). Finding relevant imaging biomarkers is necessary for identification of basic activity criteria of the disease, choosing treatment algorithms, determining treatment duration and termination criteria, and predicting the outcomes. Presence of IRF is associated with poor functional outcomes. Its presence is an indication for early beginning of treatment aimed at full resorption of the fluid with further possible careful extension of anti-VEGF therapy intervals with a regular follow-up. Degenerative intraretinal cysts developing in the background of subretinal fibrosis in absence of choroidal neovascularization (CNV) should be a sign for discontinuation of anti-VEGF therapy due to the lack of targets. Presence of SRF is associated with favorable outcomes and good treatment prognosis and is not a barrier to the extension of treatment intervals even up to the maximum of 16 weeks as described in existing randomized controlled trials, on the condition of no other CNV activity. PED with active CNV is one of the biomarkers that reveal the need for long-term aggressive therapy. In case of its size gain, it is necessary to restart the anti-VEGF treatment to prevent visual loss in the long-term. Combination of different fluid types is a sign of lasting disease history with a poor outcome prognosis. In this case, anti-VEGF treatment should be started as soon as possible with long-term fixed regimen or Treat-and-extend (T&E) with minimal suitable interval for the patient and precise monitoring of the condition of retina until complete suppression of activity. Developing a personalized approach in each case plays an important role in preserving visual functions.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Idoso , Inibidores da Angiogênese/uso terapêutico , Biomarcadores , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Prognóstico , Ranibizumab/uso terapêutico , Retina , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
5.
ACS Appl Mater Interfaces ; 12(52): 57710-57720, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-33320520

RESUMO

There is a continuing, urgent need for an ophthalmic (eye) drop for the clinical therapy of age-related macular degeneration (AMD), a leading cause of blindness. Here, we report the first formulation of an eye drop that is effective via autophagy for AMD treatment. This eye drop is based on a single natural product derivative (ACD), which is an amphiphilic molecule containing a 6-aminohexanoate group (H2N(CH2)5COO-). We demonstrate that this eye drop reverses the abnormal angiogenesis induced in a primate model of AMD that has the pathological characteristics close to that of human AMD. The ACD molecule was self-assembled in an aqueous environment leading to nanoparticles (NPs) about 9.0 nm in diameter. These NPs were encapsulated in calcium alginate hydrogel. The resulting eye drop effectively slowed the release of ACD and displayed extended release periods in both simulated blood (pH 7.4) and inflammatory (pH 5.2) environments. We show that the eye drop penetrated both the corneal and blood-eye barriers and reached the fundus. With low cellular toxicity, the drop targeted S1,25D3-membrane-associated rapid response steroid-binding protein (1,25D3-MARRS) promoting autophagy in a dose-dependent manner. In addition, the drop inhibited cell migration and tubular formation. On the other hand, when protein 1,25D3-MARRS was knocked down, the eye drop did not exhibit such inhibition functionalities. Our study indicates that the 6-aminohexanoate group on self-assembled NPs encapsulated in hydrogel leads to the positive in vivo outcomes. The present formulation offers a promising approach for clinical treatment of human AMD.


Assuntos
Produtos Biológicos/química , Degeneração Macular/tratamento farmacológico , Terapia de Alvo Molecular , Nanopartículas/química , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Animais , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Neovascularização de Coroide/complicações , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Macaca mulatta , Degeneração Macular/complicações , Degeneração Macular/patologia , Modelos Moleculares , Conformação Molecular , Soluções Oftálmicas/uso terapêutico
6.
PLoS One ; 15(12): e0244183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33378369

RESUMO

PURPOSE: To evaluate the effectiveness, safety, and treatment patterns of ranibizumab 0.5 mg in prior ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD) enrolled in the LUMINOUS™ study. PATIENTS AND METHODS: LUMINOUS, a 5-year, prospective, multicenter, observational study, recruited 30,138 adult patients (treatment-naïve or prior ranibizumab-treated or other ocular treatments) across all approved indications for ranibizumab. Patients were treated as per local ranibizumab label of participating countries. Here we report the mean change in visual acuity (VA) at Year 1, treatment exposure, overall incidence of ocular, non-ocular adverse events (AEs) and serious AEs (SAEs) in prior ranibizumab-treated nAMD patients (n = 16,167). RESULTS: At baseline, the mean (standard deviation [SD]) age of patients was 78.4 (9.0) years, 59.0% were female, and 80.0% were Caucasian. At Year 1 (n = 10,168), the mean (SD) VA change was -1.6 (12.6) letters (baseline VA: 58.3 [19.0] letters) with a mean (SD) of 4.7 (3.1) ranibizumab injections. Stratified by duration of prior ranibizumab treatment of <1 (n = 4,112), 1 to <2 (n = 2,095), 2 to <3 (n = 1,506), 3 to <4 (n = 1,123), 4 to <5 (n = 689), and ≥5 (n = 256) years, the mean (SD) VA change at Year 1 were -1.2 (13.5), -2.0 (12.3), -2.0 (11.3), -1.9 (11.8), -2.5 (10.9), and 0.0 (11.2) letters, respectively. Mean (SD) VA change in patients who received ≤6 and >6 injections over 1 year was -1.8 (13.8) and +0.5 (12.5) letters, respectively. The rate of ocular/non-ocular AEs and SAEs across all prior ranibizumab-treated patients over 5 years were 13.29%/23.02% and 0.84%/13.66%, respectively. CONCLUSIONS: Overall, regardless of the prior ranibizumab-treatment duration, VA was maintained in these patients at Year 1, and those receiving ≥6 injections showed a trend towards gaining letters. There were no new safety signals. These results may help inform routine clinical practice to appropriately treat nAMD patients with ranibizumab to achieve optimal visual outcomes.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Efeitos Adversos de Longa Duração/epidemiologia , Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Acuidade Visual
7.
Drugs Today (Barc) ; 56(11): 699-704, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33332477

RESUMO

Given the success in stabilizing vision with current anti-vascular endothelial growth factor (VEGF) options, one main target for future anti-VEGF drug development includes creating medications with longer durations of action. Achieving this goal will decrease the number of overall injections and follow-up visits required to ensure better patient compliance. The smallest anti-VEGF created so far is brolucizumab (Beovu; Novartis). It is a 26-kDa IgG single-chain antibody fragment that delivers 11 times more anti-VEGF per injection than aflibercept. Brolucizumab was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet age-related macular degeneration, and has been also approved for the same indication in Japan and the European Union in 2020. In this article, we compare brolucizumab to current FDA-approved anti-VEGF treatments, address the studies associated with brolucizumab, discuss brolucizumab's side effects, and conclude with recommendations.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Injeções Intravítreas , Japão , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão
8.
Cesk Slov Oftalmol ; 76(4): 1-3, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33086850

RESUMO

The issue of macular retinal degeneration is one of the key areas of ophthalmology. Recent advances in the targeted delivery of vascular endothelial growth factor (VEGF) suppressants have significantly impacted the patient's prognosis in the form of a significant deceleration in disease progression. Some of the drugs have gradually found their use in other indications (central retinal vein occlusion or diabetic macular edema). The following text gives a brief look at the physiology of VEGF, but not only in the eye, but throughout the human body, particularly in the context of adverse effects resulting from systemic inhibition of its effects.


Assuntos
Retinopatia Diabética , Degeneração Macular , Edema Macular , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
9.
Vestn Oftalmol ; 136(4. Vyp. 2): 207-213, 2020.
Artigo em Russo | MEDLINE | ID: mdl-32880141

RESUMO

PURPOSE: To assess the functional results of antiangiogenic therapy in patients with exudative form of age-related macular degeneration (AMD) in real clinical practice. MATERIAL AND METHODS: The study included 90 people (90 eyes) with active choroidal neovascularization (CNV) on the background of AMD. All patients were divided into 6 groups depending on the year of treatment - from 2013 to 2018, all patients were divided into 6 groups and overall the retrospective study sited at Research Institute of Eye Diseases (Moscow) lasted 8 years. All patients underwent standard ophthalmological examination including visometry, biomicroscopy and ophthalmoscopy under drug-induced mydriasis, as well as optical coherence tomography, fundus angiography and OCT-angiography. RESULTS: According to the results of the analysis of OCT data obtained from 2013 to 2017, among all patients with exudative AMD, patients with types I and II of CNV and single patients with RAP prevailed, which explains the high visual acuity - about 0.5 - in all groups after the start of the treatment (table 1 and 2). In 2018, 33.3% of patients were diagnosed with RAP (the same number of eyes as with types I and II of CNV), which can be explained by the introduction of OCT-angiography into wide clinical practice. The lack of increase in visual acuity is most likely associated with a small amount of intravitreal injections (IVI) - 4.8 IVI in the first year and 3.3 IVI in the second injection year. In patients who received more than three IVI in the first year of observation, visual acuity increased from 0.49±0.03 to 0.6±0.03 (p=0.04), in the case of less than three IVI in the first year, visual acuity was not changed, amounting to 0.42±0.1 before and 0.44±0.1 (p=0.655) after the treatment. CONCLUSIONS: Patients of all groups exhibited proportional stabilization of visual acuity, a decrease in the thickness of the retina and total macular volume. The lack of improvements of visual acuity is most likely associated with a small amount of IVI.


Assuntos
Neovascularização de Coroide/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Moscou , Estudos Retrospectivos , Tomografia de Coerência Óptica
10.
Klin Monbl Augenheilkd ; 237(11): 1312-1319, 2020 Nov.
Artigo em Inglês, Alemão | MEDLINE | ID: mdl-32869243

RESUMO

PURPOSE: Choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD) undergoing anti-VEGF therapy transforms into a fibrotic lesion. This fibrovascular transformation is associated with a great variety of functional and morphological effects. The aim of this study was to investigate the vascular morphology of fibrotic CNV, to compare it with its surrounding tissue and to identify phenotypes using optical coherence tomography angiography (OCTA). METHODS: In 18 eyes with fibrotic CNV in nAMD spectral domain OCT (SD-OCT) and OCTA were performed. The automated segmentation lines were manually adjusted. A slab from 60 µm beneath Bruch's membrane to the inner edge of the subretinal hyperreflective material was applied. Quantitative analysis of the vascular morphology was performed using skeletonized OCTA images. RESULTS: Compared to the perilesional rim, the number of segments per area was significantly lower (234.75 ± 25.68 vs. 255.30 ± 20.34 1/mm2, p = 0.0003) within the fibrovascular lesion. Two phenotypes could be identified within the lesion. The phenotypic traits of cluster 1 were few, long and thick vascular segments; Cluster 2 was characterized by many, short and thin vascular segments (number of segments per area: 219.4 ± 18.8 vs. 258.8 ± 13.2 1/mm2, p = 0.00009, segment length: 49.6 ± 2.7 vs. 45.0 ± 1.3 µm, p = 0.0002, vascular caliber: 26.6 ± 1.2 vs. 23.5 ± 1.8 µm, p = 0.003). The clusters did not differ significantly regarding visual acuity (0.52 ± 0.44 vs. 0.54 ± 0.18 logMAR, p = 0.25), differentiability of subretinal (OR = 3.43, CI = [0.30, 39.64], p = 0.6) and intraretinal fluid (OR = 5.34, CI = [0.48, 89.85], p = 0.14). Less normalized ellipsoid zone (EZ) loss could be observed in cluster 1 (131.0 ± 161.3 vs. 892.4 ± 955.6 1/m, p = 0.006). CONCLUSION: In this study the vascular morphology of fibrotic CNV was analyzed using OCTA. Differences between the lesion and a perilesional rim could be detected. Two phenotypes within the fibrovascular lesion were identified. These morphological clusters could indicate different patterns of fibrovascular transformation of the CNV under long-term anti-VEGF therapy and be useful identifying possible predictive biomarkers in future studies.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/diagnóstico por imagem , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Degeneração Macular/complicações , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/tratamento farmacológico , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/complicações , Degeneração Macular Exsudativa/diagnóstico por imagem , Degeneração Macular Exsudativa/tratamento farmacológico
11.
AAPS PharmSciTech ; 21(6): 236, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32803351

RESUMO

In recent years, with the aging of the population and the frequent use of electronic devices, many eye diseases have shown a linear upward trend, such as dry eye disease, glaucoma, cataract, age-related macular degeneration, and diabetic retinopathy. These diseases are often chronic and difficult to cure. Based on the structure and barrier of the human eye, this review describes the pathogenesis and treatments of several intractable eye diseases and summarizes the advanced ocular drug delivery systems to provide new treatment ideas for these diseases. Finally, we also look forward to the prospect of RNAi therapy in the treatment of eye diseases.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/metabolismo , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Catarata/diagnóstico , Catarata/tratamento farmacológico , Catarata/metabolismo , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/metabolismo , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/metabolismo , Oftalmopatias/diagnóstico , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Humanos , Latanoprosta/administração & dosagem , Latanoprosta/metabolismo , Degeneração Macular/tratamento farmacológico , Degeneração Macular/epidemiologia , Degeneração Macular/fisiopatologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/metabolismo , Timolol/administração & dosagem , Timolol/metabolismo , Resultado do Tratamento , Verteporfina/administração & dosagem , Verteporfina/metabolismo
13.
J Fr Ophtalmol ; 43(8): 761-769, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32622633

RESUMO

INTRODUCTION: To describe the one-year functional outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) treated with anti-VEGF agents at the Dijon University Hospital Ophthalmology Department. METHODS: Real-life interventional study including all treatment-naïve nAMD patients from January 2016 to December 2018 in the Ophthalmology Department of Dijon University Hospital. Data were retrospectively collected from the Fight Retinal Blindness! (FRB!) registry. At baseline, medical history, visual acuity (VA), type of lesion and activity on angiography and optical coherence tomography (OCT), and treatment were recorded. On follow-up, VA, lesion activity and treatment were recorded. RESULTS: Three-hundred twenty eyes of 259 patients were included, of which 65.6% were female and with a mean age of 80.1±11.1 years. Mean VA (standard deviation, SD) at baseline was 53.2 ETDRS letters (25.3). All patients received anti-VEGF injections, of which 164 eyes (51.2%), 152 eyes (47.5%) and 4 eyes (1.2%) were treated with aflibercept, ranibizumab and bevacizumab, respectively. A total of 198 eyes of 169 patients completed the 12-month follow-up, with a median (first quartile, third quartile) of 12 visits (10, 13). At one year (n=198), the overall mean VA gain [95% CI] was +3.3 ETDRS letters [0.7, 5.9] and 173 (87.4%) of the treated eyes did not lose 15 or more letters. We found no statistically significant difference in mean VA gain between aflibercept and ranibizumab. CONCLUSION: This real-world study confirmed the efficacy of anti-VEGF agents in nAMD and the feasibility of analyzing data in an international registry.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Cegueira/tratamento farmacológico , Cegueira/epidemiologia , Feminino , França/epidemiologia , Humanos , Injeções Intravítreas , Degeneração Macular/epidemiologia , Masculino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/epidemiologia , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
15.
Arch. Soc. Esp. Oftalmol ; 95(6): 263-270, jun. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-199191

RESUMO

OBJETIVO: Evaluar y comparar los resultados visuales y morfológicos de regímenes de tratamiento pro re nata (PRN) y tratar-y-extender (T&E) a tres años en la práctica clínica real. MÉTODOS: Un estudio retrospectivo de pacientes con degeneración macular vinculada a la edad neovascular (DMEN) tratadas con anti-VEGF con tres años de seguimiento continuo y sin tratamientos anti-VEGF anteriores. Se midieron la mejor agudeza visual corregida (MAVC), el espesor foveal central (EFC) y el número de inyecciones intravítreas para determinar diferencias estadísticas entre ambos grupos al inicio y a lo largo del seguimiento. RESULTADOS: Se incluyeron en el estudio un total de 240 ojos, 170 en el grupo PRN y 70 en el grupo T&E. A los 12 meses la ganancia media con respecto al inicio de MAVC (en letras ETDRS) llegó a su punto más alto en el grupo T&E (+ 6,38 ± 13,32; p = 0,25). En el grupo PRN, MAVC llegó al máximo a los tres meses y disminuyó lentamente hasta el final del seguimiento. Con ambos regímenes, desde el inicio el EFC continuó disminuyendo hasta el segundo año (PRN -138,81 [-846,7 a +162,77] y T&E -81 [-604 a +100] μm, p = 0,06). Posteriormente, el grupo T&E mantuvo esta tendencia, llegando al nivel más bajo de EFC a los 36 meses, mientras que el grupo PRN mostró un aumento en los valores de EFC (PRN -104 [-807,7 a +297] μm y T&E -103 [-575 a +244], μm p = 0,63). Los pacientes tratados con el régimen T&E recibieron un número significativamente mayor de inyecciones (PRN 16,3 ± 7,6 vs. T&E 23,9 ± 9,4, p <0,01). CONCLUSIÓN: Los resultados demostraron una tendencia de T&E a conseguir valores más altos de MAVC, llegando al máximo a los 12 meses, y grosores menores de EFC al final de tres años. A pesar del mayor número de inyecciones en el grupo T&E, la media de MAVC revirtió a los valores de base a los tres años


PURPOSE: Evaluate and compare the visual and morphological results of Pro re nata (PRN) and treat-and-extend (T&E) treatment regimens at 3 years in real world clinical practice. METHODS: Retrospective study of patients with neovascular age macular: degeneration (AMD) treated with anti-VEGF with 3 years of continuous follow-up and no previous anti-VEGF treatment. Best corrected visual acuity (BCVA), central foveal thickness (CFT) and number of intravitreal injections outcomes were tested for statistical differences between the two groups at baseline and during follow-up. RESULTS: A total of 240 eyes were included in the study, 170 in the PRN group and 70 in the T&E group. At 12 months, mean BCVA (ETDRS letters) gain from baseline was at its highest point in the T&E group (+6.38 ± 13.32; p = 0.25). In the PRN group, BCVA peaked at 3 months and slowly decreased until end of follow-up. With both regimens, from baseline, CFT continued to decrease until the second year (PRN -138.81 [-846.7 to +162.77] and T&E -81 [-604 to +100] μm, p = 0.06). After that, T&E group maintained this tendency, reaching the lowest CFT value at 36 months, whereas PRN group showed an increased in CFT values (PRN -104 [-807.7 to +297] μm and T&E -103 [-575 to +244], μm p = 0.63). Patients treated with T&E regimen received a significantly higher number of injections (PRN 16.3 ± 7.6 vs T&E 23.9 ± 9.4, p < 0.01). CONCLUSION: Our results demonstrated a trend towards for T&E to achieve higher marks in BCVA, peaking at 12 months, and lower CFT thickness at the end of three years. Despite the higher number of injections performed in the T&E group the mean BCVA reverts to baseline values at 3 years


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Degeneração Macular/tratamento farmacológico , Injeções Intravítreas/métodos , Bevacizumab/administração & dosagem , Degeneração Macular/complicações , Degeneração Macular/diagnóstico por imagem , Fundo de Olho , Tomografia de Coerência Óptica , Angiofluoresceinografia , Acuidade Visual , Resultado do Tratamento , Neovascularização de Coroide
16.
Drug Discov Ther ; 14(2): 98-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378652

RESUMO

The authors present the use of prostaglandin E1 (PGE1) for the treatment of an acute paracentral acute middle maculopathy (PAMM). A 78-year-old white female was seen with a sudden loss of vision in her left eye (OS) to 20/200 noted upon awakening. The right eye (OD) saw 20/20. A complete eye exam was done and an ocular coherent tomography revealed retinal thickening and a whitening of the inner nuclear layer in the area of the macula OS. A diagnosis of PAMM in the OS was made. Treatment was immediately started with 70 µg of PGE1 administered over 1.5 hours in the form of a skin cream. A volume of 3.5 cc of skin cream was applied in divided doses to the inner surface of the forearm, rubbed into the skin and allowed to dry. The same 70 µg of PGE1 in 3.5 cc of skin cream was repeated once the next morning. The patient began to see better the second day of treatment with a final visual acuity of 20/20. The OD was unchanged. After 14 months she was stable with no further treatment. PAMM is an ischemic process of the inner retina. PGE1, a potent vasodilator of the microcirculation, when given immediately seemed to be useful in restoring vision in this form of retinal ischemia. Treatment was immediately started with PGE1 in the form of a skin cream with visual improvement. The authors normally use PGE1 intravenously for acute ocular ischemia and would have preferred that here. Intravenous PGE1 was not available and was substituted with the skin cream of PGE1 that worked well for the patient.


Assuntos
Alprostadil/uso terapêutico , Isquemia/tratamento farmacológico , Degeneração Macular/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos , Idoso , Olho/irrigação sanguínea , Feminino , Humanos
18.
Drugs Today (Barc) ; 56(5): 311-320, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32406878

RESUMO

Wet age-related macular degeneration (w-AMD) represents the main cause of vision loss in the elderly in the western countries. The important role displayed by vascular endothelial growth factor (VEGF) in the pathogenesis of this disease has been largely demonstrated. For this reason, anti-VEGF drugs have been developed and currently are considered as the first-line treatment options in the management of w-AMD. Among the novel anti-VEGF agents studied, conbercept is a fusion protein composed of the combination between VEGF receptor domains with the Fc fragment of human immunoglobulin. It was already approved in China in 2014 for treating w-AMD. In this regard, the phase III PHOENIX trial has reported a good clinical efficacy and safety profile of conbercept for w-AMD, also by adopting a quarterly regimen. In this review, we will discuss its pharmacokinetics, pharmacodynamics, clinical efficacy, without neglecting also its safety and tolerability profile.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Macular/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Idoso , Ensaios Clínicos Fase III como Assunto , Humanos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
19.
Cochrane Database Syst Rev ; 5: CD012208, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32374423

RESUMO

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/economia , Bevacizumab/administração & dosagem , Bevacizumab/economia , Viés , Esquema de Medicação , Endoftalmite/epidemiologia , Endoftalmite/etiologia , Humanos , Injeções Intravítreas/efeitos adversos , Degeneração Macular/patologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Ranibizumab/economia , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/economia , Retina/efeitos dos fármacos
20.
Am J Ophthalmol ; 218: 59-67, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32360340

RESUMO

PURPOSE: To describe the pre-exudative stage of exudative perifoveal vascular anomalous complex (ePVAC), referred to as nonexudative PVAC (nePVAC). DESIGN: Retrospective noncomparative case series. METHODS: Patients diagnosed with nePVAC were identified at 4 retina referral centers worldwide. Multimodal retinal imaging, including structural optical coherence tomography (OCT) and OCT-angiography (OCT-A), were performed at baseline and follow-up visits. RESULTS: Six eyes (6 patients, mean 75 ± 10 years of age) were included. Unrelated chorioretinal diseases were diagnosed in the affected eyes in 5 of 6 cases. At baseline, nePVAC is characterized by microvascular abnormalities featuring an isolated, perifoveal, large intraretinal aneurysm surrounded by capillary rarefaction at OCT-A examination, without any sign of exudation with structural OCT, and without visual impairment. Four patients were followed for a mean of 21 ± 14 months. During the follow-up, 3 of 4 eyes (75%) developed signs of exudation after a mean of 15 ± 9 months, associated with metamorphopsia and visual decline at the time of exudation. Best-corrected visual acuity decreased from 20/25 to 20/40 Snellen equivalent (P = .035) and central macular thickness increased from 268 ± 27 µm to 339 ± 65 µm (P = .145). Three patients were treated with 2.3 ± 0.6 intravitreal injections of anti-vascular endothelial growth factor without significant improvement of best-corrected visual acuity or macular edema. CONCLUSIONS: nePVAC may represent the subclinical pre-exudative stage of ePVAC, notable for an absence of exudation or visual impairment. nePVAC and ePVAC should be considered as part of the same spectrum, namely PVAC. Typically, nePVAC develops signs of exudation over time, causing metamorphopsia and visual decline and therefore these lesions warrant continued close monitoring with multimodal retinal imaging.


Assuntos
Fóvea Central/irrigação sanguínea , Degeneração Macular/diagnóstico , Edema Macular/diagnóstico , Macroaneurisma Arterial Retiniano/diagnóstico , Malformações Vasculares/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Exsudatos e Transudatos , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Degeneração Macular/fisiopatologia , Edema Macular/tratamento farmacológico , Edema Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Macroaneurisma Arterial Retiniano/tratamento farmacológico , Macroaneurisma Arterial Retiniano/fisiopatologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Malformações Vasculares/tratamento farmacológico , Malformações Vasculares/fisiopatologia , Acuidade Visual/fisiologia
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