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Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: randomized, sham-controlled, multicenter study.
Li, X, Wang, N, Liang, X, Xu, G, Li, XY, Jiao, J, Lou, J, Hashad, Y, ,
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2018;(1):59-69
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Abstract
PURPOSE The purpose of this study was to evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO). METHODS This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n = 129) or sham procedure (n = 130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography. RESULTS Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (p < 0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 35%, sham: 12%; mean BCVA change from baseline was DEX: +10.6 letters, sham: +1.7 letters; and mean CRT change from baseline was DEX: -407 μm, sham: -62 μm (all p < 0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was increased intraocular pressure (IOP). Increases in IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery. CONCLUSIONS DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3-4 months after a single implant.
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The Interval between Treatments of Bevacizumab and Dexamethasone Implants for Diabetic Macular Edema Increased over Time in the BEVORDEX Trial.
Mehta, H, Fraser-Bell, S, Nguyen, V, Lim, LL, Gillies, MC
Ophthalmology. Retina. 2018;(3):231-234
Abstract
PURPOSE To report increasing retreatment interval of intravitreal bevacizumab and dexamethasone implants for diabetic macular edema (DME) in the BEVORDEX trial. DESIGN Multicenter randomized clinical trial. PARTICIPANTS Sixty-eight eyes from 47 patients who completed 2 years of follow-up. METHODS The BEVORDEX study (www.clinicaltrials.gov identifier, NCT01298076), set in Australia, was the first head-to-head trial of bevacizumab (Avastin; Genentech, South San Francisco, CA), with retreatment considered after 4 weeks, versus a slow-release dexamethasone implant (Ozurdex; Allergan Inc., Irvine, CA), with retreatment possible after 16 weeks, for center-involving DME. Study eyes were assessed every 4 weeks for retreatment according to prespecified visual acuity and central macular thickness criteria. In this post hoc analysis, changes in treatment interval over time were examined using mixed-effects regression models. We assessed whether the mean treatment interval changed over time and if this depended on baseline characteristics or the treatment received. RESULTS Of the 68 eyes from 47 patients, 67 study eyes received at least 1 retreatment (1 eye in the dexamethasone implant group did not require retreatment over 24 months). Thirty-two eyes received bevacizumab and 35 eyes received dexamethasone implants. Study eyes received a mean of 14.6 injections (standard deviation [SD], 7.8 injections) and 5.6 injections (SD, 1.4 injections) in the bevacizumab and dexamethasone groups, respectively, over 2 years. The mean retreatment interval over the 2-year follow-up period was 70.8 days (SD, 43.8 days) for the bevacizumab group and 145 days (SD, 45.4 days) for the dexamethasone implant group. The mean treatment interval increased over time for both drugs (P = 0.016), independent of which treatment was received (P = 0.808). Longer treatment interval over time was associated with younger age (P = 0.037) and better baseline visual acuity (P = 0.026), but not with gender (P = 0.907) or baseline central macular thickness (P = 0.900). CONCLUSIONS The increase in treatment interval for both intravitreal bevacizumab and dexamethasone implants over time has implications when informing patients about potential treatment burden for DME, planning intravitreal injections services, and designing future clinical trials. For drugs with a disease-modifying effect, fixed-interval dosing may not be required beyond an initial loading phase.
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Clinical Decision-Making when Treating Diabetic Macular Edema Patients with Dexamethasone Intravitreal Implants.
García-Layana, A, Figueroa, MS, Arias, L, Adán, A, Cabrera, F, Abraldes, M, Fernández-Vega, Á, Navarro, R, Cervera, E, Silva, R, et al
Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde. 2018;(2):61-72
Abstract
Diabetes mellitus (DM) is a metabolic disease frequently associated with comorbidities that include diabetic macular edema (DME). The current medical approach to treating DME involves intravitreal injections with either anti-vascular endothelial growth factors or steroids. However, the burden associated with intravitreal injections and DM-derived complications is high, underlining the need to find optimal treatment regimens. In this article we describe the considerations we apply when treating DME patients with dexamethasone intravitreal implants (Ozurdex®), particularly those that influence the clinical decision-making process during the follow-up period. These considerations are based both on the available medical literature and on our clinical experience following the use of these implants in this type of patient, the goal being to optimize the number of injections and the clinical outcome of this therapy. We also provide a general overview of the pathophysiology of DME, highlighting the inflammatory component as a rationale to use steroids in these patients.
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Efficacy of the combination neurokinin-1 receptor antagonist, palonosetron, and dexamethasone compared to others for the prophylaxis of chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.
Chow, R, Tsao, M, Chiu, L, Popovic, M, Milakovic, M, Lam, H, DeAngelis, C
Annals of palliative medicine. 2018;(2):221-233
Abstract
BACKGROUND Chemotherapy-induced nausea and vomiting (CINV), a common side effect of chemotherapy, can substantially impair a patient's quality of life, interfere with a patient's compliance with anticancer therapy, and result in the manifestation of adverse events such as electrolyte imbalance, dehydration and malnutrition. The most recent guidelines published by the Multinational Association of Supportive Care in Cancer (MASCC) and European Society of Medical Oncology (ESMO) recommend the combination of dexamethasone (DEX), a 5-hydroxytrypatmine-3 receptor antagonist (5-HT3RA), preferably palonosetron (PALO), and a neurokinin-1 receptor antagonist (NK1RA) for prophylactic treatment of CINV in patients receiving highly emetogenic chemotherapy (HEC). The aim of this review was to examine the efficacy of triple agent, as reported in randomized controlled trials (RCTs), compared to any other prophylactic treatments. METHODS A literature search was conducted in Ovid MEDLINE(R), Embase Classic & Embase, and the Cochrane Central Register of Controlled Trials. The primary endpoint was the proportion of patients achieving complete response (CR) in the acute, delayed and overall phase. Secondary endpoints included the percentage of patients who achieved complete control (CC), no nausea and no vomiting in the acute, delayed and overall phases. RESULTS A total of 17 RCTs were included in this review, of which 3,146 patients were randomized to receive NK1RA, PALO and DEX, and 2,987 patients to receive other antiemetic treatments. The combination was not superior to other treatments in five endpoints-CC and CR in the acute phase, nausea and emesis control in the delayed phase, and nausea in the overall phase-but was superior in the other 11 endpoints. When looking only at HEC and moderately emetogenic chemotherapy (MEC) studies, the combination was only superior to others in three endpoints (delayed and overall CC, and overall emesis control) in HEC setting, which is less than the nine identified endpoints (delayed and overall CR, delayed and overall CC, acute and overall nausea control, and acute, delayed and overall phases for emesis control) in the MEC setting. CONCLUSIONS The combination of NK1RA, PALO and DEX is superior in the majority of assessed endpoints of this meta-analysis. Further studies should investigate the efficacy and safety of the triple regimen compared to regimens lacking NK1RA, to add to the discussions about whether future CINV prophylaxis guidelines should include NK1RA as a first-line treatment in the MEC setting.
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Rapid response to dexamethasone intravitreal implant in diabetic macular edema.
Lo Giudice, G, Avarello, A, Campana, G, Galan, A
European journal of ophthalmology. 2018;(1):74-79
Abstract
PURPOSE To evaluate the early effects of dexamethasone (DEX) intravitreal implants in patients with diabetic macular edema (DME). METHODS This was a prospective, single-arm, interventional clinical series. Eighteen patients (18 eyes) with chronic/recalcitrant or naive DME were included. Patients underwent single DEX intravitreal implant. Clinical assessments, including ophthalmologic examination, central retinal thickness (CRT) measurement by spectral-domain optical coherence tomography (SD-OCT) scan, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were carried out at baseline, 1-3 hours, and then 3, 7, and 30 days after treatment. The main outcome was change in CRT on SD-OCT, while secondary outcome measures included visual acuity (VA) and changes in IOP following implant. RESULTS Mean CRT significantly decreased from 565 ± 171 µm at baseline to 310 ± 89 µm at end of follow-up (p<0.001), with reduction becoming evident 1-3 hours after injection. Mean BCVA also significantly improved 7 days and 30 days after treatment up to 0.14 logMAR (p<0.05). All patients had a controlled IOP after the injection with only 1/18 eyes having a transient increase in IOP during follow-up. CONCLUSIONS This is the first study showing very early effects of DEX implants on CRT reduction and VA improvement in DME.
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OCT Biomarkers as Functional Outcome Predictors in Diabetic Macular Edema Treated with Dexamethasone Implant.
Zur, D, Iglicki, M, Busch, C, Invernizzi, A, Mariussi, M, Loewenstein, A, ,
Ophthalmology. 2018;(2):267-275
Abstract
PURPOSE Identification and characterization of patients with diabetic macular edema (DME) are important for individualizing treatment and optimizing outcome. We investigated OCT biomarkers for DME treated by intravitreal dexamethasone (DEX) implant. DESIGN Multicenter, retrospective, observational cohort study. PARTICIPANTS A total of 299 eyes from 284 patients treated with DEX implant for DME (naïve, n = 209; refractory, n = 90). Baseline best-corrected visual acuity (BCVA) was between 0.3 and 1.0 on a logarithm of minimum angle of resolution visual chart. METHODS The OCT scans previous to DEX implants were evaluated for submacular fluid, size and location of cystoid changes, inner segment-outer segment (IS-OS) continuity, quantity and location of hyperreflective foci (HRF), vitreomacular interface abnormalities, and epiretinal membrane. The BCVA and central macular thickness were recorded at baseline and at 1, 2, and 4 months after treatment with DEX implants. Correlations between OCT measures and visual outcome were analyzed using the generalized estimating equations procedure. MAIN OUTCOME MEASURES The correlation between spectral-domain (SD) OCT measures at baseline and BCVA response (mean change from baseline; categorized improvement [<5, 5-9, or ≥10; Early Treatment Diabetic Retinopathy Study letters] in BCVA) after treatment with a DEX implant. RESULTS The presence of subretinal fluid (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.23-3.20; P = 0.01), absence of HRF (OR, 3.66; 95% CI, 1.40-9.62; P = 0.01), and integrity of the IS-OS layer (OR, 2.09; 95% CI, 1.30-3.37; P = 0.003) were all predictive of better visual outcome after treatment with DEX implants. Although eyes with naïve DME gained more vision than refractory eyes (P < 0.001), the predictive value of OCT findings did not differ according to this classification. CONCLUSIONS Spectral-domain OCT is useful in identifying various imaging findings in DME. Among eyes with DME, those with submacular fluid, no HRF, and a continuous IS-OS layer responded better to DEX implants than those without these features. These findings call for further study of combinations of OCT and metabolic biomarkers.
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Pre-Emptive Effect of Dexamethasone and Diclofenac Sodium Associated With Codeine on Pain, Swelling, and Trismus After Third Molar Surgery: A Split-Mouth, Randomized, Triple-Blind, Controlled Clinical Trial.
Lima, TC, Bagordakis, E, Falci, SGM, Dos Santos, CRR, Pinheiro, MLP
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 2018;(1):60-66
Abstract
PURPOSE We aimed to compare the effect of dexamethasone, 8 mg, and diclofenac sodium, 50 mg, associated with codeine, 50 mg, on the control of pain, swelling, and trismus after extraction of impacted third molars. MATERIALS AND METHODS Fifteen healthy patients with a mean age of 22.8 years (SD, 12.62 years) received a single oral dose of either drug 1 hour before each surgical procedure (left and right teeth). At 24, 48, and 72 hours after surgery, swelling was determined by use of linear measurements on the face and trismus was determined by maximal mouth opening. Postoperative pain was self-recorded by the patients using a numerical rating scale at 24-hour intervals for a period of 72 hours. Data analysis involved descriptive statistics and Shapiro-Wilk, Wilcoxon, and paired t tests (P < .05). RESULTS Dexamethasone controlled pain (P = .016) and edema (P = .08) within 48 hours better than diclofenac sodium associated with codeine. No statistically significant differences were found between drugs regarding trismus and consumption of rescue analgesics (acetaminophen). CONCLUSIONS The results of this study suggest that pre-emptive administration of dexamethasone, 8 mg, showed better control of pain and swelling in bilateral extractions of third impacted mandibular molars.
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Real-World Assessment of Dexamethasone Intravitreal Implant in DME: Findings of the Prospective, Multicenter REINFORCE Study.
Singer, MA, Dugel, PU, Fine, HF, Capone, A, Maltman, J
Ophthalmic surgery, lasers & imaging retina. 2018;(6):425-435
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Abstract
BACKGROUND AND OBJECTIVE Dexamethasone intravitreal implant (DEX) (Ozurdex; Allergan plc, Dublin, Ireland) is approved for the treatment of diabetic macular edema (DME). This study assessed the real-world effectiveness, safety, and reinjection interval of DEX in adult patients with DME. PATIENTS AND METHODS This was a phase 4, prospective, multicenter (18 U.S. sites), observational study. RESULTS The study population comprised 177 patients (180 eyes; 93.8% previously treated). Baseline mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were 54.4 letters and 424.6 μm, respectively. DEX was administered as monotherapy or with other DME therapy (55%/45%). The mean reinjection interval was 5.0 months. Mean maximum BCVA change from baseline after the first three DEX injections was +9.1 letters, +7.7 letters, and +7.0 letters, respectively (P < .001); 36.0% of eyes achieved 15-letter or greater BCVA improvement. Mean maximum CRT change from baseline was -137.7 μm (P < .001). CONCLUSION DEX used alone or with other DME therapy improved visual and anatomic outcomes in DME patients in clinical practice, with no new safety concerns. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:425-435.].
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Prevention of Stomatitis: Using Dexamethasone-Based Mouthwash to Inhibit Everolimus-Related Stomatitis.
Saigal, B, Guerra, L
Clinical journal of oncology nursing. 2018;(2):211-217
Abstract
BACKGROUND A common class-specific toxicity of mammalian target of rapamycin (mTOR) inhibitors is stomatitis. Some patients experience a severe form of mTOR inhibitor-associated stomatitis (mIAS) that can have a negative effect on nutritional status, compromise quality of life, and potentially lead to nonadherence, reducing the efficacy of cancer therapy. OBJECTIVES This article aims to address an unmet need for education about mIAS among oncology nurses and patients and to share findings about everolimus-related stomatitis from the SWISH trial. METHODS The authors reviewed the literature on mIAS and selected a case series of experiences to illustrate successes and clinical challenges that an oncology nurse might encounter when caring for patients with advanced breast cancer who may develop everolimus-related stomatitis. FINDINGS Recommendations are provided for oncology nurses to educate patients on prevention, early detection, monitoring, and management strategies to mitigate the incidence and severity of everolimus-related stomatitis.
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Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial.
Maturi, RK, Glassman, AR, Liu, D, Beck, RW, Bhavsar, AR, Bressler, NM, Jampol, LM, Melia, M, Punjabi, OS, Salehi-Had, H, et al
JAMA ophthalmology. 2018;(1):29-38
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Abstract
IMPORTANCE Some eyes have persistent diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone. OBJECTIVE To compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME. DESIGN, SETTING, AND PARTICIPANTS Phase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat. INTERVENTIONS Following the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol. MAIN OUTCOMES AND MEASURES The primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography. RESULTS Of the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of -0.5 letters (95% CI, -3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was -110 (86) μm compared with -62 (97) μm for the ranibizumab group (adjusted difference, -52; 95% CI, -82 to -22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001). CONCLUSIONS AND RELEVANCE Although its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01945866.