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1.
JAMA Netw Open ; 4(2): e2037880, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33616665

RESUMEN

Importance: Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease. Objective: To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug. Design, Setting, and Participants: This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020. Interventions: Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism). Main Outcomes and Measures: Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study. Results: A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy. Conclusions and Relevance: These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.


Asunto(s)
Altruismo , Inhibidores de la Angiogénesis/economía , Bevacizumab/economía , Conducta de Elección , Toma de Decisiones , Oftalmopatías/tratamiento farmacológico , Participación del Paciente , Proteínas Recombinantes de Fusión/economía , Afroamericanos , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Americanos Asiáticos , Bevacizumab/uso terapéutico , Estudios de Cohortes , Análisis Costo-Beneficio , Retinopatía Diabética/tratamiento farmacológico , Costos de los Medicamentos , Grupo de Ascendencia Continental Europea , Femenino , Humanos , Degeneración Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Oportunidad Relativa , Uso Fuera de lo Indicado , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
2.
Vestn Oftalmol ; 137(1): 83-93, 2021.
Artículo en Ruso | MEDLINE | ID: mdl-33610155

RESUMEN

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.


Asunto(s)
Degeneración Macular , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológico
3.
J Fr Ophtalmol ; 44(3): 299-306, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33608176

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular , Pandemias , Neovascularización Retiniana , Tiempo de Tratamiento , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Diagnóstico Tardío/estadística & datos numéricos , Progresión de la Enfermedad , Femenino , Humanos , Inyecciones Intravítreas , Degeneración Macular/diagnóstico , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Degeneración Macular/patología , Masculino , Pandemias/estadística & datos numéricos , Examen Físico/estadística & datos numéricos , Pronóstico , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/tratamiento farmacológico , Neovascularización Retiniana/epidemiología , Neovascularización Retiniana/patología , Estudios Retrospectivos , Tiempo de Tratamiento/estadística & datos numéricos , Tomografía de Coherencia Óptica , Resultado del Tratamiento , Turquia/epidemiología , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/inmunología
4.
Biomed Pharmacother ; 133: 111041, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33378949

RESUMEN

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.


Asunto(s)
Degeneración Macular/tratamiento farmacológico , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Administración Oftálmica , Animales , Antioxidantes/farmacología , Línea Celular , Modelos Animales de Enfermedad , Humanos , Yodatos , Degeneración Macular/inducido químicamente , Degeneración Macular/enzimología , Degeneración Macular/patología , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Absorción Ocular , Soluciones Oftálmicas , Estrés Oxidativo/efectos de los fármacos , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Conejos , Ratas Sprague-Dawley , Epitelio Pigmentado de la Retina/enzimología , Epitelio Pigmentado de la Retina/patología
5.
Drugs Today (Barc) ; 56(11): 699-704, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33332477

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Degeneración Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Humanos , Inyecciones Intravítreas , Japón , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión
6.
Vestn Oftalmol ; 136(6. Vyp. 2): 227-234, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-33371654

RESUMEN

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.


Asunto(s)
Neovascularización Coroidal , Degeneración Macular , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Biomarcadores , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/etiología , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Pronóstico , Ranibizumab/uso terapéutico , Retina , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual
7.
ACS Appl Mater Interfaces ; 12(52): 57710-57720, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-33320520

RESUMEN

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.


Asunto(s)
Productos Biológicos/química , Degeneración Macular/tratamiento farmacológico , Terapia Molecular Dirigida , Nanopartículas/química , Soluciones Oftálmicas/química , Soluciones Oftálmicas/farmacología , Animales , Autofagia/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Neovascularización Coroidal/complicaciones , Células Endoteliales de la Vena Umbilical Humana/citología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Macaca mulatta , Degeneración Macular/complicaciones , Degeneración Macular/patología , Modelos Moleculares , Conformación Molecular , Soluciones Oftálmicas/uso terapéutico
8.
PLoS One ; 15(12): e0244183, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33378369

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Efectos Adversos a Largo Plazo/epidemiología , Degeneración Macular/tratamiento farmacológico , Ranibizumab/uso terapéutico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Esquema de Medicación , Femenino , Humanos , Masculino , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Agudeza Visual
9.
Cesk Slov Oftalmol ; 76(4): 1-3, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33086850

RESUMEN

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.


Asunto(s)
Retinopatía Diabética , Degeneración Macular , Edema Macular , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/uso terapéutico , Retinopatía Diabética/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual
10.
Vestn Oftalmol ; 136(4. Vyp. 2): 207-213, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32880141

RESUMEN

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.


Asunto(s)
Neovascularización Coroidal/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Moscú , Estudios Retrospectivos , Tomografía de Coherencia Óptica
11.
Klin Monbl Augenheilkd ; 237(11): 1312-1319, 2020 Nov.
Artículo en Inglés, Alemán | MEDLINE | ID: mdl-32869243

RESUMEN

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.


Asunto(s)
Neovascularización Coroidal , Degeneración Macular , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/uso terapéutico , Neovascularización Coroidal/diagnóstico por imagen , Neovascularización Coroidal/tratamiento farmacológico , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Degeneración Macular/complicaciones , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/tratamiento farmacológico , Tomografía de Coherencia Óptica , Degeneración Macular Húmeda/complicaciones , Degeneración Macular Húmeda/diagnóstico por imagen , Degeneración Macular Húmeda/tratamiento farmacológico
12.
AAPS PharmSciTech ; 21(6): 236, 2020 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-32803351

RESUMEN

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.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Oftalmopatías/tratamiento farmacológico , Oftalmopatías/metabolismo , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/metabolismo , Antihipertensivos/administración & dosificación , Antihipertensivos/metabolismo , Catarata/diagnóstico , Catarata/tratamiento farmacológico , Catarata/metabolismo , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/metabolismo , Síndromes de Ojo Seco/diagnóstico , Síndromes de Ojo Seco/tratamiento farmacológico , Síndromes de Ojo Seco/metabolismo , Oftalmopatías/diagnóstico , Glaucoma/diagnóstico , Glaucoma/tratamiento farmacológico , Glaucoma/metabolismo , Humanos , Latanoprost/administración & dosificación , Latanoprost/metabolismo , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Degeneración Macular/fisiopatología , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/metabolismo , Timolol/administración & dosificación , Timolol/metabolismo , Resultado del Tratamiento , Verteporfina/administración & dosificación , Verteporfina/metabolismo
14.
J Fr Ophtalmol ; 43(8): 761-769, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32622633

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Ceguera/tratamiento farmacológico , Ceguera/epidemiología , Femenino , Francia/epidemiología , Humanos , Inyecciones Intravítreas , Degeneración Macular/epidemiología , Masculino , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/epidemiología , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/inmunología
16.
Arch. Soc. Esp. Oftalmol ; 95(6): 263-270, jun. 2020. tab, graf
Artículo en Español | IBECS | ID: ibc-199191

RESUMEN

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


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Degeneración Macular/tratamiento farmacológico , Inyecciones Intravítreas/métodos , Bevacizumab/administración & dosificación , Degeneración Macular/complicaciones , Degeneración Macular/diagnóstico por imagen , Fondo de Ojo , Tomografía de Coherencia Óptica , Angiografía con Fluoresceína , Agudeza Visual , Resultado del Tratamiento , Neovascularización Coroidal
17.
Drug Discov Ther ; 14(2): 98-99, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32378652

RESUMEN

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.


Asunto(s)
Alprostadil/uso terapéutico , Isquemia/tratamiento farmacológico , Degeneración Macular/tratamiento farmacológico , Agudeza Visual/efectos de los fármacos , Anciano , Ojo/irrigación sanguínea , Femenino , Humanos
19.
Drugs Today (Barc) ; 56(5): 311-320, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32406878

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Proteínas Recombinantes de Fusión/uso terapéutico , Anciano , Ensayos Clínicos Fase III como Asunto , Humanos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores
20.
Cochrane Database Syst Rev ; 5: CD012208, 2020 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-32374423

RESUMEN

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.


Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Degeneración Macular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/economía , Bevacizumab/administración & dosificación , Bevacizumab/economía , Sesgo , Esquema de Medicación , Endoftalmitis/epidemiología , Endoftalmitis/etiología , Humanos , Inyecciones Intravítreas/efectos adversos , Degeneración Macular/patología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Ranibizumab/administración & dosificación , Ranibizumab/economía , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/economía , Retina/efectos de los fármacos
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