New Look at Ocular Inflammation Control – Powerful and Fast-acting Twice-daily Bromfenac for a Novel Standard in the Treatment of Inflammation

2011 ◽  
Vol 05 (01) ◽  
pp. 20 ◽  
Author(s):  
Hyung Cho ◽  
Arash Mozayan ◽  
◽  
Keyword(s):  
Intraocular Pressure ◽  
Adverse Events ◽  
Cataract Surgery ◽  
Synergistic Effects ◽  
Safety Data ◽  
Ocular Inflammation ◽  
Prostaglandin E ◽  
Ophthalmic Surgery ◽  
Inflammatory Conditions ◽  
Increased Risk

Inflammation in the eye arising from various factors – including allergy, infection, injury and surgery – can have serious consequences, and can continue long after the cause is removed, resulting in permanently damaged vision. The treatment of ophthalmic inflammation after surgery has traditionally consisted of topical corticosteroids, but adverse events such as delayed healing, rise in intraocular pressure and increased susceptibility to microbial infections have driven the search for alternative treatments. Non-steroidal anti-inflammatory drugs (NSAIDs) have been used as alternatives to steroid treatments but also have limitations and cause adverse events. Bromfenac has emerged as a potent and safe treatment for inflammation after cataract surgery. Its unique chemical structure makes it a highly lipophilic molecule that penetrates all major ocular tissues in a rapid and sustained manner. It is also a potent inhibitor of the enzyme cyclo-oxygenase-2, which is believed to be the primary mediator of ocular inflammation. These properties permit less frequent dosing (twice-daily [BID]) and greater patient tolerability. A body of efficacy and safety data support use of bromfenac in this indication and it compares favourably with other NSAIDs and steroids in limiting post-operative inflammation. NSAIDs and corticosteroids have different, potentially synergistic effects. However, benefits specific to NSAIDs include lowering prostaglandin E-induced intraocular pressure elevation, no increased risk of secondary infections and stabilisation of the blood–aqueous barrier. With increasing demand for ophthalmic surgery, bromfenac and other treatments are likely to be important components in the treatment of inflammatory conditions after cataract surgery, decreasing pain and contributing to favourable visual outcomes.

Treatment of Post-operative Inflammation following Cataract Surgery – A Review

2012 ◽  
Vol 06 (02) ◽  
pp. 98 ◽  
Author(s):  
Harminder S Dua ◽  
Richa Attre ◽  
◽  
Keyword(s):  
Side Effects ◽  
Adverse Events ◽  
Cataract Surgery ◽  
Healthcare Providers ◽  
Surgical Techniques ◽  
Ocular Inflammation ◽  
Effective Control ◽  
Loteprednol Etabonate ◽  
Design Modification

Inflammation after cataract surgery, which can be persistent, remains an undesirable consequence despite many advances in surgical techniques. Although corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) have traditionally been used to treat inflammation, prophylactically as well as post-operatively, there are no established guidelines for the treatment of inflammation induced by cataract surgery. The long-term use of corticosteroids has raised safety concerns, especially with regard to elevated intraocular pressure (IOP). This limitation of traditional corticosteroids led to the development of C-20 ester corticosteroids through retrometabolic drug design. This design modification allows the corticosteroid to be active at its site of action and then undergo predictable hydrolysis to inactive metabolites, resulting in reduced side effects. A review of studies published in the last 10 years indicates that C-20 ester corticosteroids provide effective control of post-cataract surgery inflammation without the elevation of IOP. Loteprednol etabonate ophthalmic suspension 0.5 % is the only topical C-20 ester corticosteroid approved for use in the treatment of corticosteroid-responsive inflammatory conditions including post-operative ocular inflammation. This corticosteroid, alone or in combination with NSAIDs, may provide effective and safe inflammation control, especially for high-risk patients, and may overcome concerns regarding side effects associated with traditional C-20 ketone corticosteroids. Ocular inflammation after cataract surgery presents healthcare providers with a treatment dilemma. While corticosteroids are traditionally the therapy of choice for inflammation, their long-term use for managing ocular inflammation can produce significant adverse events. This article discusses whether C-20 ester corticosteroids, alone or in combination with NSAIDs, offer effective treatment of post-cataract surgery inflammation while minimising adverse events.

Meta-analysis of anti-VEGF class adverse events from three double-blind (db), placebo (pbo)-controlled phase III trials with IV aflibercept (Afl).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3579-3579 ◽  
Author(s):  
Josep Tabernero ◽  
Carmen Joseph Allegra ◽  
Philippe R Rougier ◽  
Giorgio Scagliotti ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Safety Data ◽  
Dose Intensity ◽  
Phase Iii ◽  
Double Blind ◽  
Anti Vegf ◽  
Increased Risk ◽  
Grade 3

3579 Background: Three db, pbo-controlled studies were conducted with IV Afl in metastatic cancer patients (pts) (colorectal [CRC], Afl + FOLFIRI [WCGC 2011, abstract O-0024]; lung [LC], Afl + docetaxel [WCLC 2011, abstract 511]; and pancreatic [PC], Afl + gemcitabine [WCGC 2009 abstract O-0006]). Each study used the same weekly Afl dose intensity (4 mg/kg q2w for CRC and PC; 6 mg/kg q3w for LC). A safety meta-analysis of anti-VEGF class adverse events (AEs) was performed on data from these studies. Methods: A fixed-effect logistic regression model was used, including study, treatment, and study-by-treatment interaction factors as covariates to test the consistency of treatment effect across studies for each of the considered AE. When no evidence of heterogeneity of treatment effects was found across studies, relative risks (RRs) and 95% confidence intervals (CIs) were estimated. Summary incidences (% of pts) and RR are presented for NCI grade 3-4 events. Results: Safety data from a total of 2662 pts (Afl, 1333; pbo, 1329) were included for analysis. Among pts treated with Afl, 0.4 and 0.5% experienced grade 4 hypertension and nephrotic syndrome, respectively. Conclusions: The addition of Afl to concurrent chemotherapies did not increase the risk of VTE. The risk of grade 3-4 anti-VEGF class AEs was increased when adding Afl to concurrent chemotherapies. This increased risk was statistically significant only for hypertension, proteinuria, and hemorrhage. Further analyses, when more data are available, should improve the precision of these results. [Table: see text]

Safety and Efficacy of Ranibizumab and Bevacizumab for the Treatment of Neovascular Age-related Macular Degeneration

2012 ◽  
Vol 06 (01) ◽  
pp. 34 ◽  
Author(s):  
Victor Chong ◽  
Peter K Kaiser ◽  
Paul Mitchell ◽  
◽  
◽  
...  
Keyword(s):  
Adverse Events ◽  
Macular Degeneration ◽  
Half Life ◽  
Safety Data ◽  
Significant Risk ◽  
Age Related Macular Degeneration ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Age Related ◽  
Increased Risk

Ocular anti-vascular endothelial growth factor (VEGF) therapy represents a major breakthrough in the treatment of patients with neovascular age-related macular degeneration (nvAMD). The anti-VEGF agents, ranibizumab and bevacizumab, are both widely used in the treatment of nvAMD although bevacizumab has not yet received regulatory approval for intraocular use. Bevacizumab costs considerably less than ranibizumab when administered as an intraocular injection, which has led to widespread use and studies comparing the efficacy and safety of the two drugs. Bevacizumab shares identical pharmacology with ranibizumab although structural differences result in differences in receptor affinity and rates of drug clearance. While estimates of the vitreous half-life of ranibizumab vary, it is shorter than that of bevacizumab. Furthermore, the serum half-life of bevacizumab is about 20 days, more than twice that of ranibizumab and this has led to speculation that it may present a greater risk of systemic adverse effects. Considerable clinical trial evidence exists relating to the efficacy and safety of ranibizumab. The Comparison of age-related macular degeneration treatments trials (CATT) study of the two drugs found efficacy to be equivalent for the as needed versus as needed and monthly versus monthly comparisons. Ranibizumab as needed was equivalent to monthly ranibizumab, though the bevacizumab as needed was not equivalent to monthly bevacizumab. A greater number of serious adverse events (SAEs) occurred with bevacizumab. However, the study was insufficiently powered to identify differences in drug-related adverse events. Intravitreal injection of bevacizumab is associated with a low but significant risk of acute intraocular inflammation, shown to result in significant visual loss in some patients. Finally, there are issues related to fractionating of bevacizumab that has lead to sporadic cases of blindness worldwide. The increased risk for both systemic and ocular adverse events may influence the cost-effectiveness ratio of the two drugs based on health economic models. Further comparative studies and continuous monitoring of safety data are required to examine the incidence of adverse events.

scholarly journals Suicidality and other severe psychiatric events with duloxetine: Re-analysis of safety data from a placebo-controlled trial for juvenile fibromyalgia

2020 ◽  
pp. 1-9
Author(s):  
Michael P. Hengartner ◽  
Martin Plöderl
Keyword(s):  
Adverse Events ◽  
Psychiatric Disorders ◽  
Additional Data ◽  
Controlled Trial ◽  
Journal Article ◽  
Safety Data ◽  
Serious Adverse Events ◽  
Juvenile Fibromyalgia ◽  
Increased Risk ◽  
Supplementary Material

BACKGROUND: In antidepressant trials for pediatric patients with depression or anxiety disorders, the risk of suicidal events and other severe psychiatric adverse events such as aggression and agitation is increased with antidepressants relative to placebo. OBJECTIVE: To examine whether largely mentally healthy adolescents treated for a non-psychiatric condition are also at increased risk of suicidality and other severe psychiatric disorders. METHODS: This is a re-analysis of a placebo-controlled duloxetine trial for juvenile fibromyalgia based on the main journal article and additional data published in the online supplementary material and on ClinicalTrials.gov. Both serious adverse events related to psychiatric disorders and adverse events leading to treatment discontinuation were defined as severe treatment-emergent psychiatric adverse events. RESULTS: We found that a significant portion of adolescents had treatment-emergent suicidal ideation and behaviour as well as other severe psychiatric adverse events with duloxetine, but no such events were recorded on placebo. The incidence of severe treatment-emergent psychiatric adverse events was statistically significantly higher with duloxetine as compared to placebo. CONCLUSIONS: Antidepressants may put adolescents at risk of suicidality and other severe psychiatric disorders even when the treatment indication is not depression or anxiety.

Meta-analysis of anti-VEGF class adverse events from three double-blind (Db) placebo (Pbo)-controlled phase III trials with IV aflibercept (Afl).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 561-561 ◽  
Author(s):  
Carmen Joseph Allegra ◽  
Josep Tabernero ◽  
Philippe Rougier ◽  
Giorgio Scagliotti ◽  
Philip Agop Philip ◽  
...  
Keyword(s):  
Adverse Events ◽  
Metastatic Cancer ◽  
Meta Analysis ◽  
Safety Data ◽  
Dose Intensity ◽  
Phase Iii ◽  
Double Blind ◽  
Anti Vegf ◽  
Increased Risk ◽  
Grade 3

561 Background: Three Db Pbo controlled studies were conducted with IV Afl in metastatic cancer patients [colorectal (CRC) Afl+FOLFIRI (WCGC 2011 abstract O-0024), lung (LC) Afl+docetaxel (WCLC 2011, abstract 511) and pancreatic (PC) Afl+gemcitabine (WCGC 2009 abstract O-0006)]. Each study used the same weekly Afl dose intensity (4 mg/kg q2w for CRC and PC; 6mg/kg q3w for LC). A safety meta-analysis of anti-VEGF class adverse events (AE) was performed on data from these studies. Methods: A fixed-effect logistic regression model was used, including study, treatment and study-by-treatment interaction factors as covariates to test the consistency of treatment effect across studies for each of the considered AE. When no evidence of heterogeneity of treatment effects was found across studies, relative risks (RR) and 95% confidence intervals (CI) were estimated. Summary incidences (% of patients [pts]) and RR are presented for NCI grade 3-4 events. Results: Safety data from total of 2,662 pts (Afl: 1,333; Pbo: 1,329) were included for analysis (Table). Among pts treated with Afl, 0.4 and 0.5% experienced grade 4 hypertension and nephrotic syndrome, respectively. Conclusions: The addition of Afl to concurrent chemotherapies did not increase the risk of VTE. The risk of grade 3-4 anti-VEGF class AEs was increased when adding Afl to concurrent chemotherapies. This increased risk was statistically significant (**) only for hypertension, proteinuria and hemorrhage. Further analyses, when more data are available, should improve the precision of these results. Studies were sponsored by Sanofi NCT00561470 , NCT00532155 , and NCT00574275 . [Table: see text]

P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pellicori ◽  
A Pernille Ofstad ◽  
D Fitchett ◽  
C Zeller ◽  
C Wanner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Adverse Events ◽  
Repeated Measures ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Safety Data ◽  
Increased Risk ◽  
Outcome Trial

Abstract Background The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years. Purpose To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline. Methods We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model. Results A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA. Conclusions In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.

scholarly journals Uveitis-glaucoma-hyphema syndrome associated with an in-the-bag square-edge intraocular lens

2019 ◽  
Vol 2 (4) ◽  
pp. 283-287
Author(s):  
Jin Yang ◽  
Xiaodi Qiu ◽  
Lei Cai ◽  
Qi Fan ◽  
Anjian Wang ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Cataract Surgery ◽  
Intraocular Lens ◽  
Diagnostic Procedure ◽  
Ocular Inflammation ◽  
Local Hospital ◽  
Blurred Vision ◽  
Iol Implantation ◽  
Elevated Intraocular Pressure ◽  
One Year

Abstract A 54-year-old woman presented with recurrent redness and blurred vision of the left eye with elevated intraocular pressure (IOP) for one year. She was treated as “iridocyclitis” and ``Posner-Schlossman syndrome'' at the local hospitals. However, the patient developed intermittent ocular inflammation and hyphema. Patient had a cataract surgery and intraocular lens (IOL) implantation in the left eye one year before at the local hospital. A diagnostic procedure was performed and the possible pathogenesis was discussed.

scholarly journals Adverse Events Among Young Adults Following a Third Dose of Measles-Mumps-Rubella Vaccine

2020 ◽  
Author(s):  
Mona Marin ◽  
Amy Parker Fiebelkorn ◽  
Daoling Bi ◽  
Laura A Coleman ◽  
Janell Routh ◽  
...  
Keyword(s):  
Young Adults ◽  
Adverse Events ◽  
Injection Site ◽  
Median Duration ◽  
Safety Data ◽  
The United States ◽  
Rubella Vaccine ◽  
Related Symptom ◽  
Increased Risk ◽  
Healthcare Visit

Abstract Background A third measles-mumps-rubella vaccine (MMR) dose (MMR3) is recommended in the United States for persons at increased risk for mumps during outbreaks. MMR3 is also likely given to persons who might have received 2 doses of MMR but lack documentation. Since MMR3 safety data are limited, we describe adverse events in persons receiving MMR3 in a nonoutbreak setting. Methods Young adults with 2 documented MMR doses were administered MMR3. From 2 weeks before until 4 weeks after MMR3 receipt, participants reported daily on 11 solicited, common symptoms potentially associated with MMR. Weekly rate differences in post- vs prevaccination (baseline) were evaluated by Poisson regression. Baseline rates were subtracted from postvaccination rates of significantly different symptoms to estimate the number and percentage of participants with excess risk for symptoms post-MMR3. Descriptive analyses were performed for 3 postvaccination injection-site symptoms. Results The 662 participants were aged 18–28 years (median = 20 years); 56% were women. Headache, joint problems, diarrhea, and lymphadenopathy rates were significantly higher postvaccination vs baseline. We estimate that 119 participants (18%) reported more symptoms after MMR3 than prevaccination. By symptom, 13%, 10%, 8%, and 6% experienced increased symptoms of headache, joint problems, diarrhea, and lymphadenopathy, respectively, after MMR3. The median onset was Days 3–6 postvaccination; the median duration was 1–2 days. One healthcare visit for a potential vaccination-related symptom (urticaria) was reported. Injection-site symptoms were reported by 163 participants (25%); the median duration was 1–2 days. Conclusions Reported systemic and local events were mild and transient. MMR3 is safe and tolerable among young adults.

scholarly journals Clinical outcomes of combined Preserflo Microshunt implantation and cataract surgery in open-angle glaucoma patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
José M. Martínez-de-la-Casa ◽  
Federico Saenz-Francés ◽  
Laura Morales-Fernandez ◽  
Lucia Perucho ◽  
Carmen Mendez ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Adverse Events ◽  
Cataract Surgery ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Open Label ◽  
Sample Mean ◽  
Open Label Study ◽  
Label Study ◽  
Wound Leakage

AbstractTo assess the effectiveness and safety of the Preserflo Microshunt (PMS) implantation combined with cataract surgery in open-angle glaucoma (OAG) patients. Retrospective, open-label study conducted on insufficiently controlled OAG patients, who underwent a PMS implant procedure with mitomycin-C 0.2%, either alone or in combination with cataract surgery, and were followed for at least 12 months. Success was defined as an intraocular pressure (IOP) ≤ 18 mmHg and a reduction of at least 20% without (complete) or with (qualified) hypotensive medication. Fifty-eight eyes were included in the study, 35 eyes underwent PMS alone and 23 underwent PMS + Phaco. In the overall study sample, mean IOP was significantly lowered from 21.5 ± 3.3 mmHg at baseline to 14.6 ± 3.5 mmHg at month 12 (p < 0.0001). The IOP was significantly reduced in both groups; p < 0.0001 each, respectively. Ocular hypotensive medication was significantly reduced (p < 0.0001) in both groups. No significant differences were observed in IOP lowering or medication reduction between groups. At month 12, 62.1% eyes were considered as complete success and 82.8% eyes as qualified success. The most common adverse events were device close-to-endothelium, conjunctival fibrosis, and wound leakage. PMS, either alone or in combination with phacoemulsification, may be considered as a valuable option for treating OAG patients.

scholarly journals Loteprednol Etabonate in Ocular Inflammation

2011 ◽  
Vol 04 (01) ◽  
pp. 57 ◽  
Author(s):  
John Sheppard ◽  
Jimmy Bartlett ◽  
◽  
Keyword(s):  
Clinical Trial Data ◽  
Ocular Inflammation ◽  
Viral Reactivation ◽  
Ocular Surgery ◽  
Loteprednol Etabonate ◽  
Inflammatory Conditions ◽  
Seasonal Allergic Conjunctivitis ◽  
Increased Risk ◽  
Pressure Development ◽  
Low Incidence

Treatment of ocular inflammation imposes a major medical and economic burden. Topical corticosteroids are effective in reducing ocular inflammation but are limited by adverse events including elevation of intraocular pressure, development of cataracts, inhibition of wound healing, and increased risk for infection or viral reactivation. Loteprednol etabonate (LE) is a unique C-20 ester corticosteroid designed to produce a predictable therapeutic effect with a low incidence of side effects. Clinical trial data have demonstrated its efficacy in a variety of ocular inflammatory conditions including giant papillary conjunctivitis, seasonal allergic conjunctivitis, anterior uveitis, superficial punctate keratitis, and dry eye syndrome. These data have been corroborated by much clinical experience. Furthermore, LE may be used to reduce the inflammation associated with ocular surgery and thus improve surgical outcomes without the risks associated with traditional ketone corticosteroid use.

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