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1.
Indian J Ophthalmol ; 68(10): 2291-2293, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32971697

RESUMO

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the "cytokine-storm" as the pathogenesis for systemic manifestations of COVID-19.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Infecções Oculares Virais/virologia , Pneumonia Viral/virologia , Vasculite Retiniana/virologia , Oclusão da Veia Retiniana/virologia , Administração Oral , Inibidores da Angiogênese/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada , Infecções Oculares Virais/diagnóstico , Infecções Oculares Virais/tratamento farmacológico , Angiofluoresceinografia , Glucocorticoides/uso terapêutico , Humanos , Injeções Intravítreas , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Ranibizumab/uso terapêutico , Vasculite Retiniana/diagnóstico , Vasculite Retiniana/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
2.
Med Sci (Paris) ; 36(8-9): 753-762, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32821052

RESUMO

Macular edema is an increase in volume of the central area of the retina, responsible for visual acuity. Visual symptoms handicap the lives of millions of patients with macular edema secondary to chronic and sometimes acute retinal disease. Proteins that neutralize the vascular endothelial growth factor (VEGF) pathway or glucocorticoids, at the cost of repeated intraocular injections over years, limit visual symptoms. A better understanding of why and how edema forms and how therapeutic molecules exert an anti-edematous effect will help prevent this disabling and blinding retinal complication from occurring.


Assuntos
Edema Macular/etiologia , Edema Macular/terapia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia , Acuidade Visual/efeitos dos fármacos , Acuidade Visual/fisiologia
3.
Cochrane Database Syst Rev ; 8: CD004004, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32844399

RESUMO

BACKGROUND: Radiotherapy has been proposed as a treatment for new vessel growth in people with neovascular age-related macular degeneration (AMD). OBJECTIVES: To examine the effects of radiotherapy on neovascular AMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers and checked references of included studies. We last searched the databases on 4 May 2020.  SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with choroidal neovascularisation (CNV) secondary to AMD. DATA COLLECTION AND ANALYSIS: We used standard procedures expected by Cochrane. We graded the certainty of the evidence using GRADE. We considered the following outcomes at 12 months: best-corrected visual acuity (BCVA) (loss of 3 or more lines, change in visual acuity), contrast sensitivity, new vessel growth, quality of life and adverse effects at any time point.  MAIN RESULTS: We included 18 studies (n = 2430 people, 2432 eyes) of radiation therapy with dosages ranging from 7.5 to 24 Gy. These studies mainly took place in Europe and North America but two studies were from Japan and one multicentre study included sites in South America. Three of these studies investigated brachytherapy (plaque and epimacular), the rest were studies of external beam radiotherapy (EBM) including one trial of stereotactic radiotherapy. Four studies compared radiotherapy combined with anti-vascular endothelial growth factor (anti-VEGF) with anti-VEGF alone. Eleven studies gave no radiotherapy treatment to the control group; five studies used sham irradiation; and one study used very low-dose irradiation (1 Gy). One study used a mixture of sham irradiation and no treatment. Fifteen studies were judged to be at high risk of bias in one or more domains. Radiotherapy versus no radiotherapy There may be little or no difference in loss of 3 lines of vision at 12 months in eyes treated with radiotherapy compared with no radiotherapy (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.64 to 1.04, 811 eyes, 8 studies, I2 = 66%, low-certainty evidence). Low-certainty evidence suggests a small benefit in change in visual acuity (mean difference (MD) -0.10 logMAR, 95% CI -0.17 to -0.03; eyes = 883; studies = 10) and average contrast sensitivity at 12 months (MD 0.15 log units, 95% CI 0.05 to 0.25; eyes = 267; studies = 2). Growth of new vessels (largely change in CNV size) was variably reported and It was not possible to produce a summary estimate of this outcome. The studies were small with imprecise estimates and there was no consistent pattern to the study results (very low-certainty evidence). Quality of life was only reported in one study of 199 people; there was no clear difference between treatment and control groups (low-certainty evidence). Low-certainty evidence was available on adverse effects from eight of 14 studies. Seven studies reported on radiation retinopathy and/or neuropathy. Five of these studies reported no radiation-associated adverse effects. One study of 88 eyes reported one case of possible radiation retinopathy. One study of 74 eyes graded retinal abnormalities in some detail and found that 72% of participants who had radiation compared with 71% of participants in the control group had retinal abnormalities resembling radiation retinopathy or choroidopathy. Four studies reported cataract surgery or progression: events were generally few with no consistent evidence of any increased occurrence in the radiation group. One study noted transient disturbance of the precorneal tear film but there was no evidence from the other two studies that reported dry eye of any increased risk with radiation therapy. None of the participants received anti-VEGF injections. Radiotherapy combined with anti-VEGF versus anti-VEGF alone People receiving radiotherapy/anti-VEGF were probably more likely to lose 3 or more lines of BCVA at 12 months compared with anti-VEGF alone (RR 2.11, 95% CI 1.40 to 3.17, 1050 eyes, 3 studies, moderate-certainty). Most of the data for this outcome come from two studies of epimacular brachytherapy (114 events) compared with 20 events from the one trial of EBM. Data on change in BCVA were heterogenous (I2 = 82%). Individual study results ranged from a small difference of -0.03 logMAR in favour of radiotherapy/anti-VEGF to a difference of 0.13 logMAR in favour of anti-VEGF alone (low-certainty evidence). The effect differed depending on how the radiotherapy was delivered (test for interaction P = 0.0007). Epimacular brachytherapy was associated with worse visual outcomes (MD 0.10 logMAR, 95% CI 0.05 to 0.15, 820 eyes, 2 studies) compared with EBM (MD -0.03 logMAR, 95% CI -0.09 to 0.03, 252 eyes, 2 studies). None of the included studies reported contrast sensitivity or quality of life. Growth of new vessels (largely change in CNV size) was variably reported in three studies (803 eyes). It was not possible to produce a summary estimate and there was no consistent pattern to the study results (very low-certainty evidence). For adverse outcomes, variable results were reported in the four studies. In three studies reports of adverse events were low and no radiation-associated adverse events were reported. In one study of epimacular brachytherapy there was a higher proportion of ocular adverse events (54%) compared to the anti-VEGF alone (18%). The majority of these adverse events were cataract. Overall 5% of the treatment group had radiation device-related adverse events (17 cases); 10 of these cases were radiation retinopathy. There were differences in average number of injections given between the four studies (1072 eyes). In three of the four studies, the anti-VEGF alone group on average received more injections (moderate-certainty evidence). AUTHORS' CONCLUSIONS: The evidence is uncertain regarding the use of radiotherapy for neovascular AMD. Most studies took place before the routine use of anti-VEGF, and before the development of modern radiotherapy techniques such as stereotactic radiotherapy. Visual outcomes with epimacular brachytherapy are likely to be worse, with an increased risk of adverse events,  probably related to vitrectomy. The role of stereotactic radiotherapy combined with anti-VEGF is currently uncertain. Further research on radiotherapy for neovascular AMD may not be justified until current ongoing studies have reported their results.


Assuntos
Degeneração Macular/radioterapia , Viés , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Terapia Combinada/métodos , Olho/efeitos da radiação , Humanos , Lesões por Radiação/complicações , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/efeitos da radiação
4.
Cochrane Database Syst Rev ; 7: CD009510, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633861

RESUMO

BACKGROUND: Branch retinal vein occlusion (BRVO) is one of the most commonly occurring retinal vascular abnormalities. The most common cause of visual loss in people with BRVO is macular oedema (MO). Grid or focal laser photocoagulation has been shown to reduce the risk of visual loss. Limitations to this treatment exist, however, and newer modalities may have equal or improved efficacy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) has recently been used successfully to treat MO resulting from a variety of causes. OBJECTIVES: To investigate the efficacy and gather evidence from randomised controlled trials (RCTs) on the potential harms of anti-vascular endothelial growth factor (VEGF) agents for the treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); MEDLINE Ovid; Embase Ovid; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. The date of the last search was 12 June 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating BRVO. Eligible trials had to have at least six months' follow-up where anti-VEGF treatment was compared with another treatment, no treatment, or placebo. We excluded trials where combination treatments (anti-VEGF plus other treatments) were used; and trials that investigated the dose and duration of treatment without a comparison group (other treatment/no treatment/sham). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data using standard methodological procedures expected by Cochrane. The primary outcome was the proportion of participants with an improvement from baseline in best-corrected visual acuity of greater than or equal to 15 letters (3 lines) on the Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six months and 12 months of follow-up. The secondary outcomes were the proportion of participants who lost greater than or equal to 15 ETDRS letters (3 lines) and the mean visual acuity (VA) change at six and 12 months, as well as the change in central retinal thickness (CRT) on optical coherence tomography from baseline at six and 12 months. We also collected data on adverse events and quality of life (QoL). MAIN RESULTS: We found eight RCTs of 1631 participants that met the inclusion criteria after independent and duplicate review of the search results. These studies took place in Europe, North America, Eastern Mediterranean region and East Asia. Included participants were adults aged 18 or over with VA of 20/40 or worse. Studies varied by duration of disease but permitted previously treated eyes as long as there was sufficient treatment-free interval. All anti-VEGF agents (bevacizumab, ranibizumab and aflibercept) and steroids (triamcinolone and dexamethasone) were included. Overall, we judged the studies to be at moderate or unclear risk of bias. Four of the eight studies did not mask participants or outcome assessors, or both. One trial compared anti-VEGF to sham. At six months, eyes receiving anti-VEGF were significantly more likely to have a gain of 15 or more ETDRS letters (risk ratio (RR) 1.72, 95% confidence interval (CI) 1.19 to 2.49; 283 participants; moderate-certainty evidence). Mean VA was better in the anti-VEGF group at six months compared with control (mean difference (MD) 7.50 letters, 95% CI 5.29 to 9.71; 282 participants; moderate-certainty evidence). Anti-VEGF also proved more effective at reducing CRT at six months (MD -57.50 microns, 95% CI -108.63 to -6.37; 281 participants; lower CRT is better; moderate-certainty evidence). There was only very low-certainty evidence on adverse effects. There were no reports of endophthalmitis. Mean change in QoL (measured using the National Eye Institute Visual Functioning Questionnaire VFQ-25) was better in people treated with anti-VEGF compared with people treated with sham (MD 7.6 higher score, 95% CI 4.3 to 10.9; 281 participants; moderate-certainty evidence). Three RCTs compared anti-VEGF with macular laser (total participants = 473). The proportion of eyes gaining 15 or more letters was greater in the anti-VEGF group at six months (RR 2.09, 95% CI 1.44 to 3.05; 2 studies, 201 participants; moderate-certainty evidence). Mean VA in the anti-VEGF groups was better than the laser groups at six months (MD 9.63 letters, 95% CI 7.23 to 12.03; 3 studies, 473 participants; moderate-certainty evidence). There was a greater reduction in CRT in the anti-VEGF group compared with the laser group at six months (MD -147.47 microns, 95% CI -200.19 to -94.75; 2 studies, 201 participants; moderate-certainty evidence). There was only very low-certainty evidence on adverse events. There were no reports of endophthalmitis. QoL outcomes were not reported. Four studies compared anti-VEGF with intravitreal steroid (875 participants). The proportion of eyes gaining 15 or more ETDRS letters was greater in the anti-VEGF group at six months (RR 1.67, 95% CI 1.33 to 2.10; 2 studies, 330 participants; high-certainty evidence) and 12 months (RR 1.76, 95% CI 1.36 to 2.28; 1 study, 307 participants; high-certainty evidence). Mean VA was better in the anti-VEGF group at six months (MD 8.22 letters, 95% CI 5.69 to 10.76; 2 studies, 330 participants; high-certainty evidence) and 12 months (MD 9.15 letters, 95% CI 6.32 to 11.97; 2 studies, 343 participants; high-certainty evidence). Mean CRT also showed a greater reduction in the anti-VEGF arm at 12 months compared with intravitreal steroid (MD -26.92 microns, 95% CI -65.88 to 12.04; 2 studies, 343 participants; moderate-certainty evidence). People receiving anti-VEGF showed a greater improvement in QoL at 12 months compared to those receiving steroid (MD 3.10, 95% CI 0.22 to 5.98; 1 study, 307 participants; moderate-certainty evidence). Moderate-certainty evidence suggested increased risk of cataract and raised IOP with steroids. There was only very low-certainty evidence on APTC events. No cases of endophthalmitis were observed. AUTHORS' CONCLUSIONS: The available RCT evidence suggests that treatment of MO secondary to BRVO with anti-VEGF improves visual and anatomical outcomes at six and 12 months.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Edema Macular/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab/administração & dosagem , Humanos , Injeções Intravítreas , Fotocoagulação a Laser , Terapia a Laser , Edema Macular/etiologia , Edema Macular/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Terapia de Salvação/métodos , Esteroides/administração & dosagem , Acuidade Visual/efeitos dos fármacos
5.
Middle East Afr J Ophthalmol ; 27(1): 4-9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32549717

RESUMO

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare retinal vasculopathy that might cause subretinal and/or vitreous hemorrhages. Although the primary etiology is still unknown, choroidal neovascularization is mainly involved in the pathogenesis. The main risk factors are age and systemic hypertension. Ancillary testing such as fluorescein angiography, indocyanine green angiography and ultrasonography can be of great value for diagnosing this entity and distinguishing PEHCR from other lesions as choroidal melanoma and retinal vasoproliferative tumor. Various treatments have been reported including photocoagulation, cryotherapy, intravitreal injection of anti-vascular endothelial growth factor (Anti-VEGF) and surgical intervention as pars plana vitrectomy. This review handles an up-to-date perspective regarding PEHCR.


Assuntos
Hemorragia Retiniana/etiologia , Hemorragia Vítrea/etiologia , Inibidores da Angiogênese/uso terapêutico , Corantes/administração & dosagem , Crioterapia , Angiofluoresceinografia , Humanos , Verde de Indocianina/administração & dosagem , Injeções Intravítreas , Fotocoagulação a Laser , Hemorragia Retiniana/diagnóstico , Hemorragia Retiniana/terapia , Fatores de Risco , Tomografia de Coerência Óptica , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Vitrectomia , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/terapia
7.
J Chin Med Assoc ; 83(9): 817-821, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32568969

RESUMO

As the coronavirus disease 2019 (COVID-19, also called severe acute respiratory syndrome coronavirus-2) outbreak accelerates, vigorous and diverse efforts were made in developing treatment strategies. In addition to direct acting agents, increasing evidence showed some potential adjuvant therapies with promising efficacy against COVID-19. These therapies include immunomodulators (i.e. intravenous immunoglobulin, thymosin α-1, interleukin [IL]-6, tocilizumab, cyclosporine, thalidomide, fingolimod), Chinese medicines (i.e. glycyrrhizin, baicalin, Xuebijing), anti-vascular endothelial growth factors (bevacizumab), estrogen modulating drugs, statins, and nutritional supplements (i.e. vitamins A, B, C, D, E and zinc). This article reviewed the pharmacological development of potential adjuvants for COVID-19 treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Suplementos Nutricionais , Humanos , Fatores Imunológicos/uso terapêutico , Medicina Tradicional Chinesa , Apoio Nutricional , Pandemias , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
8.
Br J Cancer ; 123(5): 694-697, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32572174
10.
PLoS One ; 15(5): e0232353, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369500

RESUMO

IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. METHOD: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Degeneração Retiniana/tratamento farmacológico , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Atrofia , Bevacizumab/uso terapêutico , Feminino , Seguimentos , Humanos , Interpretação de Imagem Assistida por Computador , Injeções Intravítreas , Masculino , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Retiniana/diagnóstico por imagem , Epitélio Pigmentado da Retina/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Resultado do Tratamento
12.
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
13.
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
14.
PLoS One ; 15(4): e0232494, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353052

RESUMO

BACKGROUND AND OBJECTIVE: To develop a semi-automated, machine-learning based workflow to evaluate the ellipsoid zone (EZ) assessed by spectral domain optical coherence tomography (SD-OCT) in eyes with macular edema secondary to central retinal or hemi-retinal vein occlusion in SCORE2 treated with anti-vascular endothelial growth factor agents. METHODS: SD-OCT macular volume scans of a randomly selected subset of 75 SCORE2 study eyes were converted to the Digital Imaging and Communications in Medicine (DICOM) format, and the EZ layer was segmented using nonproprietary software. Segmented layer coordinates were exported and used to generate en face EZ thickness maps. Within the central subfield, the area of EZ defect was measured using manual and semi-automated approaches via a customized workflow in the open-source data analytics platform, Konstanz Information Miner (KNIME). RESULTS: A total of 184 volume scans from 74 study eyes were analyzed. The mean±SD area of EZ defect was similar between manual (0.19±0.22 mm2) and semi-automated measurements (0.19±0.21 mm2, p = 0.93; intra-class correlation coefficient = 0.90; average bias = 0.01, 95% confidence interval of limits of agreement -0.18-0.20). CONCLUSIONS: A customized workflow generated via an open-source data analytics platform that applied machine-learning methods demonstrated reliable measurements of EZ area defect from en face thickness maps. The result of our semi-automated approach were comparable to manual measurements.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Monitoramento de Medicamentos/métodos , Aprendizado de Máquina , Edema Macular/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Adulto , Bevacizumab/uso terapêutico , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Macula Lutea/diagnóstico por imagem , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Oclusão da Veia Retiniana/complicações , Tomografia de Coerência Óptica , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fluxo de Trabalho
15.
Eur J Ophthalmol ; 30(4): 795-804, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32389030

RESUMO

Wet age-related macular degeneration is a chronic condition culminating, in most cases, in blindness. The introduction of anti-angiogenic agents in 2006 has represented a major breakthrough in the treatment of the disease, but timely and effective treatment with regular follow-up and monitoring is mandatory to stabilize and preserve visual acuity. In clinical practice, however, appropriate therapy provision is frequently challenged by economic and organizational issues that result in suboptimal visual outcomes and increased incidence of legal blindness. International Guidelines have defined a diagnostic and therapeutic pathway to ensure the best practice in wet age-related macular degeneration management, but reference parameters to evaluate and compare the performance of Retina Centers are lacking. To address the appropriateness of wet age-related macular degeneration management in Italy, a multidisciplinary panel of ten experts gathered in three meetings. They defined three sets of indicators and relative benchmark values that each Center should comply with to ensure patients optimal care already from the first access: (a) clinical intervention indicators, to determine the possible Center's deviation from the diagnostic and therapeutic pathway; (b) outcome indicator, to evaluate the socioeconomic impact of the healthcare systems' performance; (c) management indicators, to test the size of the gap between the Center's supply and demand. Once the indicators have been analyzed, healthcare systems can plan actions to improve appropriateness and monitor their effects. However, to put this in practice, a concerted effort by all parts involved in healthcare provision is required, together with adequate systems to analyze clinical and administrative documentation.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Benchmarking , Prova Pericial , Feminino , Humanos , Injeções Intravítreas , Masculino , Lista de Medicamentos Potencialmente Inapropriados , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia
16.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1149-1156, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: covidwho-121183

RESUMO

PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy's Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.


Assuntos
Infecções por Coronavirus/prevenção & controle , Injeções Intravítreas , Oftalmologia/organização & administração , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Doenças Retinianas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Betacoronavirus , Desinfecção , Humanos , Equipamento de Proteção Individual
17.
Invest Ophthalmol Vis Sci ; 61(3): 49, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32232346

RESUMO

Purpose: Energy compromise underpins wet age-related macular degeneration (wAMD) pathogenesis, but the relationship between glucose metabolism and the disease remains unclear. Here, we characterized aqueous humor (AH) to elucidate glucose-related metabolic signatures in patients with wAMD. Methods: In total, 25 eyes of 25 patients with wAMD were divided into phakic (15 eyes), pseudophakic (10 eyes), and intravitreal injections of ranibizumab (13 eyes) wAMD groups. Twenty patients with cataract (21 eyes) served as controls. Ultrahigh-performance liquid chromatography tandem mass spectrometry was used to quantitatively characterize AH. Results: Twenty-one metabolites related to glucose metabolism were identified in AH from 45 patients. Tricarboxylic acid (TCA)-related metabolic substrates, including citrate, were detected in AH and were significantly increased in AMD (P < 0.01) and AMD pseudophakic groups (P < 0.05). In contrast, α-ketoglutarate levels were decreased in the AMD group (P < 0.05). The α-ketoglutarate/citrate ratio was significantly decreased, corresponding to 71.71% and 93.6% decreases in the AMD (phakic and pseudophakic) groups as compared with controls (P < 0.001), revealing a significant positive correlation with glutamine. A lower mean glutamine and higher glutamate level were detected in AMD cases compared with controls. No significant differences were observed for lactic acid or other Krebs cycle metabolites. Intravitreal injection significantly alleviated mean central foveal thickness but did not significantly alter metabolites. Conclusions: Compromised glucose TCA cycle and altered glutamine metabolism are implicated in the AH metabolism in wAMD. These findings highlight potential treatments for alleviating wAMD from a metabolic perspective.


Assuntos
Humor Aquoso/metabolismo , Neovascularização de Coroide/metabolismo , Glucose/metabolismo , Degeneração Macular Exsudativa/metabolismo , Idoso , Inibidores da Angiogênese/uso terapêutico , Estudos de Casos e Controles , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Cromatografia Líquida , Ciclo do Ácido Cítrico/fisiologia , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Ranibizumab/uso terapêutico , Espectrometria de Massas em Tandem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico
18.
Eur J Ophthalmol ; 30(3): 586-594, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32347762

RESUMO

PURPOSE: To report 12-month outcomes of a Polish National Treatment Program using aflibercept and ranibizumab in eyes with wet, age-related macular degeneration in routine clinical practice. MATERIAL AND METHODS: This was a non-randomized, retrospective, observational multicenter study. Anonymous data contained in the electronic Therapeutic Program Monitoring System were utilized in this study. RESULTS: The study population consisted of 2828 eyes from 2718 patients. The median age was 76.0 [70.0, 81.0] years; 61.7% were female. Best corrected visual acuity increased from 58.86 [50.05, 69.95] letters to 65.1 [50.1, 73.9] letters (p < 0.001). The median change in best corrected visual acuity was 0.0 [-4.0, 12.2] letters: 2.9 [-2.9, 15.1] letters for treatment-naïve eyes and 0.0 [-4.0, 8.8] letters for those continuing treatment (p < 0.001). The median central retinal thickness was significantly reduced from 341.0 [281.0, 422.0] to 275.0 [221.0, 344.0] µm (p < 0.001). The median number of visits was 9.0 [8.0, 9.0]. The median number of injections was 7.0 [6.0, 8.0]: 8.0 [7.0, 8.0] for treatment-naïve eyes and 6.0 [5.0, 7.0] for those continuing treatment (p < 0.001). CONCLUSION: Eyes treated as part of the Polish therapeutic program gained functional stability and morphological improvement. Treatment-naïve eyes showed the greatest functional benefit.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Polônia , Retina/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/fisiopatologia
19.
Life Sci ; 252: 117670, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298741

RESUMO

Deregulation of angiogenesis is a key reason for tumor growth and progression. Several anti-angiogenic drugs in clinical practice attempt to normalize abnormal tumor vasculature. Unfortunately, these drugs are ineffective due to the development of resistance in patients after drug holidays. A sizable literature suggests that resistance to these anti-angiogenic drugs occurs due to various compensatory mechanisms of tumor angiogenesis. Therefore, we describe different compensatory mechanisms of tumor angiogenesis, and explain why intussusceptive angiogenesis (IA), is a crucial mechanism of compensatory angiogenesis in tumors which resist anti-VEGF (vascular endothelial growth factor) therapies. IA is often overlooked due to the scarcity of experimental models. Therefore, we examine data from existing experimental models and our novel ex-ovo model of angiogenesis in chick embryos, and explain the important genes and signaling pathways driving IA. Using bio-informatic analyses of major genes regulating conventional sprouting angiogenesis (SA) and intussusceptive angiogenesis, we provide fresh insights on the 'angiogenic switch' which regulates the transition from SA to IA. Finally, we examine the interplay between molecules regulating SA, IA, and molecules known to promote tumor progression. Based on these analyses, we conclude that intussusceptive angiogenesis (IA) is a promising therapeutic target for developing effective anti-cancer treatment regimes.


Assuntos
Inibidores da Angiogênese/farmacologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Animais , Embrião de Galinha , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias/irrigação sanguínea , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
20.
Zhonghua Yan Ke Za Zhi ; 56(4): 246-249, 2020 Apr 11.
Artigo em Chinês | MEDLINE | ID: mdl-32306615

RESUMO

Retinal vein occlusion (RVO) is the consequence of obstruction of retinal vein system caused by a variety of etiologies. Its ocular complications include macular edema, retinal ischemia and neovascular glaucoma. Although many drugs for management of RVO are available, some doctors do not fully understand the exact purpose of each treatment. This article starts from the etiology evaluation of RVO, emphasizing that, besides systemic etiology and risk factor management, the treatment of RVO should focus on the three major complications at the same time, rather than just dealing with macular edema. Meanwhile, a regular follow-up for observing the changes of the degree of retinal ischemia is important for whole course management. Anti-vascular endothelial growth factor therapy, the first-line treatment option of RVO, can not only reduce macular edema, but also prevent the complications caused by retinal ischemia and create opportunities for further laser photocoagulation. Laser photocoagulation has an irreplaceable value in the comprehensive treatment of ischemic RVO. Glucocorticoid intraocular implants should not be used alone in the treatment of macular edema secondary to RVO. (Chin J Ophthalmol, 2020, 56:246-249).


Assuntos
Oclusão da Veia Retiniana/terapia , Inibidores da Angiogênese/uso terapêutico , Glaucoma/etiologia , Humanos , Isquemia/etiologia , Fotocoagulação , Edema Macular/etiologia , Oclusão da Veia Retiniana/complicações , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
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