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FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.
Choi, M, Yun, C, Oh, JH, Kim, SW
Retina (Philadelphia, Pa.). 2022;(1):129-137
Abstract
PURPOSE To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. METHODS In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. RESULTS Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. CONCLUSION The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.
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Bevacizumab for treating Hereditary Hemorrhagic Telangiectasia patients with severe hepatic involvement or refractory anemia.
Vázquez, C, Gonzalez, ML, Ferraris, A, Bandi, JC, Serra, MM
PloS one. 2020;(2):e0228486
Abstract
OBJECTIVE To report our clinical experience with bevacizumab in a cohort of Hereditary Hemorrhagic Telangiectasia (HHT) patients with severe hepatic involvement and/or refractory anemia. METHODS Observational, ambispective study of the Institutional Registry of HHT at Hospital Italiano de Buenos Aires. Patients were treated with bevacizumab due to iron deficiency refractory anemia secondary to nasal/gastrointestinal bleeding and/or high output cardiac failure. We describe basal clinical data, bevacizumab schedules, efficacy outcomes and adverse events. Wilcoxon signed ranks test and longitudinal analysis were conducted. RESULTS Twenty adult patients were included from July 2013 to June 2019. Clinical indications were: 13 for anemia, 4 for heart failure and 3 for both. In the anemia group, median pretreatment hemoglobin was 8.1 g/dl [IQR: 7.2-8.4] and median transfusion requirement was 4 units [2-6]. In heart failure group, pretreatment median cardiac index was 4.5 L/min/m2 [4.1-5.6] and cardiac output was 8.3 L/min [7.5-9.2]. Bevacizumab 5 mg/kg/dose every 2 weeks for 6 applications was scheduled. By the end of induction, median hemoglobin at 3 months was 10.9 g/dl [9.5-12.8] (p = 0.01) and median transfusion requirement 0 units [0-1] (p<0.01), and this effect was more or less sustained during a year. Regarding heart failure group, two patients had complete hemodynamic response and achieved liver transplantation and two had partial response. No serious adverse events were registered. CONCLUSION Bevacizumab is a promising line of treatment for HHT patients with refractory anemia. For patients with high output cardiac failure, bevacizumab may be useful as bridge therapy awaiting for liver transplantation.
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Real-world management of treatment-naïve diabetic macular oedema: 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study.
Shimura, M, Kitano, S, Muramatsu, D, Fukushima, H, Takamura, Y, Matsumoto, M, Kokado, M, Kogo, J, Sasaki, M, Morizane, Y, et al
The British journal of ophthalmology. 2020;(12):1755-1761
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Abstract
BACKGROUND/AIMS: To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). METHODS Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. RESULTS Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. CONCLUSION For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing.
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Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment.
Natarajan, G, Shankaran, S, Nolen, TL, Sridhar, A, Kennedy, KA, Hintz, SR, Phelps, DL, DeMauro, SB, Carlo, WA, Gantz, MG, et al
Pediatrics. 2019;(2)
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OBJECTIVE Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). RESULTS The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. CONCLUSIONS In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.
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Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN study.
Busch, C, Fraser-Bell, S, Zur, D, Rodríguez-Valdés, PJ, Cebeci, Z, Lupidi, M, Fung, AT, Gabrielle, PH, Giancipoli, E, Chaikitmongkol, V, et al
Acta diabetologica. 2019;(7):777-784
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AIMS: To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. METHODS A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) ≤ 0.1 logMAR (≥ 20/25 Snellen) and central subfield thickness (CST) > 250 µm with intra- and/or subretinal fluid seen on optical coherence tomography. RESULTS A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss < 5 letters) at 12 months (treated: 58.1%; non-treated: 73.4%). In non-treated eyes with stable VA within the first 6 months, VA was maintained throughout the follow-up in most cases (86.3%). In non-treated eyes with VA loss ≥ 5 letters within 6 months (36.7%), further observation led to worse visual outcome than treatment (- 4.2 vs. - 7.8 letters, p = 0.013). In eyes in which treatment was initiated at baseline (n = 102), treatment with 8-12 anti-VEGF injections led to better visual outcome compared to treatment with less injections (- 0.3 ± 3.6 letters vs. - 3.8 ± 6.2 letters, p = 0.003). CONCLUSION In a real-world setting, the majority of DME patients with very good VA maintained vision at 12 months, regardless of whether the DME was treated or not. This study supports close observation of eyes with DME and very good VA with consideration of treatment when a one line drop in vision is observed.
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Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series.
Hillier, RJ, Connor, AJ, Shafiq, AE
The British journal of ophthalmology. 2018;(2):260-264
Abstract
BACKGROUND Intravitreal bevacizumab (IVB) has emerged as an effective treatment modality for the management of retinopathy of prematurity (ROP) where the disease is severe and posterior. Despite evidence of systemic vascular endothelial growth factor suppression and concerns about how this might affect the developing neonate, the optimal dose is unknown to date. We report our experience of using ultra-low-dose (0.16 mg) IVB, one-quarter of the 'standard' dose that has widely been reported in the treatment of ROP. METHODS A retrospective observational case series of consecutive infants who underwent ultra-low-dose IVB injection for the management of ROP at a regional neonatal intensive care unit in the North East of England, between November 2013 and August 2016. RESULTS 29 eyes of 15 infants underwent IVB injection. We defined 'treatment success' as complete regression of retinopathy and vascularisation into (or laser ablation of) zone 3. Primary success (in response to IVB 0.16 mg alone) was observed in 23/29 eyes (79.3%). Secondary success (where additional treatment was required) was observed in 27/29 eyes (93.1%). One infant died of respiratory disease during follow-up. Retreatment occurred in 6/29 eyes (20.6%). Retreatments occurred at a mean of 9.8 weeks after initial IVB (range 6-15) and at a mean of 44 weeks postmenstrual age (range 40-50). CONCLUSION 0.16 mg IVB is effective in the treatment of severe and posterior ROP, with no adverse ocular outcomes occurring in our series.
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Integrating geriatric assessment in the first line chemotherapy treatment in older patients with metastatic colorectal cancer: Results of a prospective observational cohort study (AVAPLUS).
Decoster, L, Kenis, C, Naessens, B, Houbier, G, De Man, M, Lambrecht, G, Monsaert, E, Moons, V, Vergauwe, P, Prenen, H, et al
Journal of geriatric oncology. 2018;(2):93-101
Abstract
OBJECTIVES This study aims to investigate the use of chemotherapy with or without bevacizumab in older patients with metastatic colorectal cancer (mCRC) in current daily practice and to identify predictive parameters for treatment-related outcomes. PATIENTS AND METHODS This is a Belgian multi-centre, observational cohort study. Patients≥70years old with mCRC considered suitable for first-line chemotherapy were eligible for inclusion. At baseline geriatric screening and assessment was performed. Treatment choice was at the discretion of the investigator. Treatment duration, Progression Free Survival (PFS) and safety were recorded. RESULTS Between August 2011 and July 2013, 252 patients with mCRC were included of which 50.8% were treated with bevacizumab. Median treatment duration was 5.5months and median PFS was 8.9months. Approximately 50% of patients experienced severe adverse events, most frequently diarrhea. In multivariate analysis, baseline Eastern Cooperative Oncology Group (ECOG)-performance status (PS) was predictive for treatment duration (p=0.0047), PFS (p<0.0001) and severe toxicity and baseline nutritional status for PFS (p=0.0007). In patients with a good ECOG-PS, nutritional status was predictive for PFS. CONCLUSIONS In current daily practice in Belgium, half of older patients with colorectal cancer treated with chemotherapy also receive bevacizumab. Nearly half of older patients presented with severe toxicity during treatment. Baseline nutritional status is a predictive marker for PFS. Patients with a baseline ECOG-PS≥2 have shorter PFS and higher risk of severe toxicity and should therefore be treated with caution.
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TREATMENT PATTERNS AND 2-YEAR VISION OUTCOMES WITH BEVACIZUMAB IN DIABETIC MACULAR EDEMA: An Analysis From a Large U.S. Integrated Health Care System.
Fong, DS, Luong, TQ, Contreras, R, Jimenez, JJ, Custis, PH, Patel, V, Campbell, JH
Retina (Philadelphia, Pa.). 2018;(9):1830-1838
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PURPOSE To assess health care utilization and vision outcomes over 2 years in patients receiving bevacizumab treatment in clinical practice for diabetic macular edema. METHODS Patients with newly diagnosed diabetic macular edema who received an intravitreal bevacizumab injection within 12 months of initial diagnosis were identified from Kaiser Permanente's 350,000 patients with diabetes mellitus treated between 2008 and 2013. Snellen best-corrected visual acuity (BCVA), number of intravitreal injections, and patient characteristics were abstracted from the electronic record. The main outcome measure was change in BCVA. RESULTS Three hundred and nine patients met the inclusion criteria and had 2 years of follow-up after their first bevacizumab injection. These patients had a mean of 3.1 injections (range, 1-17) during the 2-year follow-up. Mean BCVA improvement was 5.4 letters at 12 months and 5.3 letters at 24 months. Only 29.8% of patients demonstrated ≥3 lines of vision improvement from baseline, whereas 12.3% had ≥3 lines of vision loss from baseline at 24 months. CONCLUSION This is the largest U.S. clinical practice-based study of bevacizumab use in diabetic macular edema. Consistent with national studies, the frequency of injection was low. Average BCVA improvement was lower than in anti-vascular endothelial growth factor trials. Significant BCVA improvement was achieved in approximately 30% of patients with newly diagnosed diabetic macular edema.
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Outcome of Bevacizumab Therapy in Patients with Recurrent Glioblastoma Treated with Angiotensin System Inhibitors.
Johansen, MD, Urup, T, Holst, CB, Christensen, IJ, Grunnet, K, Lassen, U, Friis, S, Poulsen, HS
Cancer investigation. 2018;(9-10):512-519
Abstract
PURPOSE Antihypertensive therapy may improve bevacizumab efficacy in cancer patients. We examined efficacy and toxicity of angiotensin system inhibitors (ASI) and other antihypertensive drugs in bevacizumab treated recurrent glioblastoma patients. METHODS We retrospectively combined a national prescription registry with a clinical database with recurrent glioblastoma patients (n = 243). RESULTS Patients who initiated ASI after bevacizumab (n = 26) showed a tendency towards improved progression-free survival and overall survival (OS) with hazard rate (HR) reductions (HR = 0.70 and HR = 0.79, respectively). Calcium antagonists during bevacizumab therapy significantly improved OS (HR = 0.57). CONCLUSIONS Overall the study supports a potential beneficial effect of antihypertensive treatment on prognosis of bevacizumab treated glioblastoma patients.
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Vitreous levels of placental growth factor correlate with activity of proliferative diabetic retinopathy and are not influenced by bevacizumab treatment.
Al Kahtani, E, Xu, Z, Al Rashaed, S, Wu, L, Mahale, A, Tian, J, Abboud, EB, Ghazi, NG, Kozak, I, Gupta, V, et al
Eye (London, England). 2017;(4):529-536
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PurposePlacental growth factor (PlGF) is a member of the VEGF family that plays an important role in experimental models of diabetic retinopathy and retinal neovascularization. We aimed to investigate whether vitreous levels of PlGF correlated with proliferative diabetic retinopathy (PDR) status, VEGF levels, and bevacizumab treatment. We also analysed PDR membranes to confirm the presence of the PlGF receptor, FLT1, in endothelial cells.MethodsThis was a case-control study: undiluted vitreous fluid samples were obtained from 28 active PDR patients without preoperative bevacizumab treatment, 21 active PDR patients with preoperative bevacizumab treatment, 18 inactive PDR patients, and 21 control patients. PlGF and VEGF levels in samples were determined by enzyme-linked immunosorbent assay. Immunohistochemistry for FLT1 was performed on human PDR membranes.ResultsCompared to control, vitreous PlGF levels were higher in both active PDR without bevacizumab (P<0.0001) and with bevacizumab (P<0.0001). There was no significant difference in PlGF between active PDR patients without and with bevacizumab (P=0.56). Compared to active PDR, PlGF levels were significantly reduced in inactive PDR (P=0.004). PlGF levels were highly correlated with VEGF levels in active PDR. VEGFR1 was expressed in endothelial cells in human PDR membranes.ConclusionThe strong correlation of PlGF levels with PDR disease status and expression of FLT1 in human PDR membranes suggest that PlGF has a pathogenic role in proliferative diabetic retinopathy. Therapeutic targeting of PlGF with agents like aflibercept may be beneficial.