Topical Nonsteroidal Anti-inflammatory Drugs Research Articles

Prescribing Patterns and Costs Associated with Postoperative Eye Drop Use in Medicare Beneficiaries Undergoing Cataract Surgery

To determine costs and prescribing patterns of postoperative eye drops for cataract surgery and estimate potential savings of generic or therapeutic drug substitutions. Retrospective, cross-sectional analysis. Medicare beneficiaries aged ≥65 years with Part D coverage who underwent cataract surgery in2016. Medicare Part D claims were used to extract information on eye drop prescriptions that were filled during the postoperative period of cataract surgery. Savings from generic or therapeutic drug substitutions were estimated for brand medications. Total cost of postoperative eye drops for cataract surgery and physician and patient factors associated with medication cost. Postoperative eye drops were prescribed in 2016 to 88% of 591 733 Medicare beneficiaries who underwent cataract surgery during that calendar year, with brand medications accounting for 57.5% of prescription volume. The overall cost totaled more than $167 million, 76.5% of which was attributable to use of brand medications. The mean costs of medications were $228 and $324 for those undergoing 1 and 2 surgeries, respectively. Topical antibiotics (89%) were the most commonly prescribed drug class by volume, followed by topical steroids (86%) and nonsteroidal anti-inflammatory drugs (66%), and accounted for 26%, 37%, and 36% of the total cataract surgery eye drop cost, respectively. Use of therapeutic and generic alternatives could have resulted in cost savings of as much as $118 million, or 70% of the total cost of postoperative eye drops. In adjusted analysis, patient factors associated with increased eye drop cost included older age, female gender, and race or ethnicity. Physician characteristics associated with increased eye drop cost included female gender, greater number of years in practice, practicing in metropolitan versus nonmetropolitan areas, and practicing in the Northeast versus the South and in the South versus the Midwest. The cost to the Centers for Medicare and Medicaid Services for eye drops prescribed for postoperative use after cataract surgery in 2016 was approximately $170 million. In the absence of evidence of clinical superiority of expensive versus less costly options, substantial opportunity exists to improve the value of care delivered to Medicare beneficiaries.

Agarose-Based Gel-Phase Microextraction Technique for Quick Sampling of Polar Analytes Adsorbed on Surfaces.

Sampling and extraction of chemical residues present on flat or curved surfaces as well as touch-sensitive objects are challenging. Hydrogels are characterized by high mechanical flexibility and water content. Thus, they are an ideal medium for transferring water-soluble analytes from a sampled surface to the next stage of an analytical workflow. Here, we demonstrate gel-phase microextraction (GPME), in which disks of blended hydrogels are utilized to lift traces of water-soluble substances adsorbed on surfaces. The protocol has been optimized in a series of tests involving fluorometric and mass spectrometric measurements. Compared with the pure agarose hydrogel, most of the tested blended hydrogels provide a higher efficiency for the sampling/extraction of a model analyte, fluorescein. The blended hydrogel disks are incorporated into three-dimensional (3D)-printed acrylonitrile–butadiene–styrene chips to create easy-to-use sampling probes. We exemplify the suitability of this improved GPME approach in sampling chemical residues present on the skin, glass, and daily use objects. In these tests, the extracts were analyzed on a triple quadrupole mass spectrometer fitted with an electrospray ion source operated in the positive- and negative-ion modes. The method enabled the detection of diclofenac on excised porcine skin fragments exposed to a topical nonsteroidal anti-inflammatory drug and sweat residues (lactic acid) left on surfaces touched by humans. The limits of detection for diclofenac and lactic acid in hydrogel extract were 6.4 × 10–6 and 2.1 × 10–5 M, respectively. In a model experiment, conducted using the presented approach, the amount of lactic acid on a glass slide with fingerprints was estimated to be ∼1.4 × 10–7 mol cm–2.

The importance of preoperative topical non-steroidal antiinflammatory agents in cataract surgery- an open label prospective randomised comparative study

Introduction: Intraoperative miosis is a problem which can lead to various complications that may adversely affect the outcome of cataract surgery. Topical non-steroidal anti-inflammatory drugs (NSAIDs) have been found to be helpful in reducing the intraoperative miosis. We tried to compare the effectiveness of two such molecules bromfenac and nepafenac. Objective: To compare the effectiveness of topical bromfenac (0.09%) and nepafenac (0.1%) in maintaining mydriasis and controlling immediate post-operative inflammation in cataract surgery. Methods: This is a prospective, randomised, open-label, comparative study of patients with senile cataract posted for cataract extraction and intra-ocular lens (IOL) implantation. The patients were randomised into 3 groups: topical moxifloxacilin 0.5% alone (control group or group A), topical bromfenac 0.09% + moxifloxacilin 0.5% (group B) and topical nepafenac 0.1% + moxifloxacilin 0.5% (group C). The drops were started one day before surgery. Mean pupil diameter was measured before starting surgery and after implanting IOL. Slit lamp examination was done on first postoperative day to look for anterior chamber reaction. The values were compared among the 3 groups. Results: The total loss of mean pupillary diameter was significant (p < 0.0001) in control group (25.87%) as compared to bromfenac (3.51%) and nepafenac (3.81%) group. Post-operative inflammation was significantly less (p <0.0001) in bromfenac and nepafenac group as compared to that of control group. Loss of mydriasis and post-operative inflammation was similar in both bromfenac and nepafenac group. Conclusion: Both bromfenac and nepafenac given topically prior to cataract surgery are equally effective in maintaining mydriasis during surgery as well as in controlling immediate postoperative inflammation.

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

DIAGNOSIS DAN TATALAKSANA KOMPREHENSIF OSTEOARTRITIS

NSAID use among residents in 68 residential aged care facilities 2014 to 2017: An analysis of duration, concomitant medication use, and high-risk conditions.

People in residential aged care are at increased risk of adverse events from nonsteroidal anti-inflammatory drugs (NSAIDs) due to their age and health status, but little is known about use of NSAIDs in this setting. We aimed to estimate the prevalence of NSAID use by route, differences by high-risk conditions, prevalence of concurrent proton pump inhibitor (PPI) use, and prevalence of the "triple whammy" combination (oral NSAID, diuretic, and angiotensin-converting-enzyme inhibitor or angiotensin receptor antagonist). We conducted a dynamic cohort study using medication administration data from 68 residential aged care facilities (RACFs) during 2014 to 2017. Descriptive statistics and regression were used to estimate the proportion of residents who used NSAIDs, NSAIDs long term, NSAIDs with PPIs, and the triple whammy combination. Ten thousand three hundred sixty-seven residents were included. Two thousand four hundred fourteen (23.3%) used at least one NSAID: 756 (7.3%) used only oral, 1326 (12.8%) used only topical, and 332 (3.2%) used both topical and oral NSAIDs. One thousand five hundred forty two (14.8%) used an NSAID long term, a majority of which only used topical NSAIDs 933/1542 (60.5%). Age, sex, and health status were associated with greater variation in long-term topical use relative to oral NSAID use. A majority of oral NSAID users concomitantly used a PPI, which varied according to age, sex, and health status. Among residents with any oral NSAID use, 182/1088 (16.7%) had triple whammy medication use. Targeted interventions to reduce NSAID use among RACF residents, to reduce triple whammy medication use, and increase PPI use for long-term oral NSAID users are warranted.

Evaluation iontophoretic delivery of a cationic ketoprofen prodrug for treating nociceptive symptoms in monosodium iodoacetate induced osteoarthritic rat model.

Topical nonsteroidal anti-inflammatory drugs have been used in treatment of osteoarthritis but their efficacy is marginal. One major reason is because of limited drug direct penetration to affected joint and muscle tissues from the topical application. The main purpose of this study was to evaluate a new topical treatment through enhancing the direct drug penetration to local muscle and joint tissues for improving topical treatment of osteoarthritis. A cationic prodrug, ketoprofen choline chloride (KCC) was synthesized for iontophoretic topical delivery. Anodal iontophoretic delivery of KCC and cathodal iontophoretic delivery of ketoprofen to the knee of live hairless rats were evaluated and the drug concentrations in the joint and muscle tissues over the time were determined. In addition, a knee osteoarthritis rat model was induced with intra-articular injection of monosodium iodoacetate solution. Anodal iontophoretic delivery of KCC, cathodal iontophoretic delivery of ketoprofen, or anodal iontophoretic delivery of sodium chloride were applied to the affected knee joint of each rat group, respectively. Knee joint pain was evaluated through a hind paw weight bearing study and knee joint inflammation was evaluated through measuring of the knee diameter. Iontophoretic delivery of KCC showed much higher drug concentration in the knee joint and muscle tissues, compared to iontophoretic delivery of ketoprofen. Treatment of rat knee joint with anodal iontophoresis of KCC also showed significant pain relief and knee inflammation reduction comparing to the control group, while treatment results from cathodal iontophoresis of ketoprofen were mostly not significantly different from the control group.

Evidence-Based Recommendations on the Pharmacological Management of Osteoarthritis and Chronic Low Back Pain: An Asian Consensus

The overall burden of chronic musculoskeletal pain in Asian countries will continue to increase as the population ages, as will the demand for safe and effective pain management. Currently available Asian guidelines are mostly outdated and targeted only to primary care. Implementation of international guidelines may be unsuitable for Asian patients due to cultural, local economic and regulatory factors. With the aim of developing Asian-specifi c consensus recommendations for the pharmacological management of osteoarthritis (OA) pain and chronic low back pain (cLBP), we convened to review and discuss recent available evidence for pharmacotherapy, clinical experiences, and current practice challenges they face in the region, including challenges in opioid use. Taking these into consideration, we provided general recommendations for the overall assessment and management of OA pain and cLBP. The strength of the recommendations regarding the use of pharmacological agents was assessed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system. Where evidence is confl icting or limited, we made no recommendation pending the availability of further evidence. We recommend topical non-steroidal anti-infl ammatory drugs (NSAIDs) as a fi rst-line pharmacological treatment of OA pain, while oral NSAIDs should be considered as a fi rst-line pharmacological treatment of cLBP. Acetaminophen has been commonly used as the fi rst-line treatment for OA pain and cLBP, but its long-term use is not recommended based on recent evidence. These consensus recommendations are not prescriptive, and serve as a guide for decision-making in clinical practice. The optimal management of OA pain and cLBP should ultimately be individualized to each patient.

Treatment of central serous chorioretinopathy with topical NSAIDs.

PurposeCentral serous chorioretinopathy (CSCR) is a common retinopathy that is often observed until resolution. The purpose of this study is to evaluate the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs) on timing of CSCR recovery.MethodsAn IRB-approved retrospective review was conducted on patients that had been diagnosed with a new-onset, symptomatic case of CSCR. Patients were either observed only (13 untreated eyes) or treated with topical bromfenac or nepafenac (14 eyes) over an average of about a 4–5 week follow-up period.ResultsThere was no statistical significance between central macular thickness (CMT) and visual acuity of treatment and control groups at the initial presentation. However, at the follow-up visit, CMT reductions in the treatment group were significantly higher than in the control group (p<0.006).ConclusionUse of topical NSAIDs in the treatment of acute CSCR leads to a faster rate of reduction in the subretinal fluid volume over a follow-up period of a few weeks.

A Comparison of Treatment Effects for Nonsurgical Therapies and the Minimum Clinically Important Difference in Knee Osteoarthritis: A Systematic Review.

The minimum clinically important difference (MCID) was developed to ascertain the smallest change in an outcome that patients perceive as beneficial. The objectives of the present review were (1) to compare the MCIDs for pain assessments used among guidelines and meta-analyses investigating different nonsurgical therapies for knee osteoarthritis and (2) to compare the effect estimates of different nonsurgical interventions against a single commonly-utilized MCID threshold. Systematic and manual searches were conducted to identify guidelines and meta-analyses evaluating pain outcomes for nonsurgical knee osteoarthritis interventions. Individual treatment effects for pain were presented on a common scale (the standardized mean difference [SMD]). To evaluate the perception of the relative benefit of each nonsurgical treatment, the variation in MCIDs selected from the published MCID literature was assessed. Thirty-seven guidelines and meta-analyses were included. MCIDs were often presented as an SMD or a mean difference (MD) on a validated scale and varied in magnitude across sources. This analysis demonstrated that intra-articular hyaluronic acid, intra-articular corticosteroids, and acetaminophen all had relatively larger effect sizes than topical nonsteroidal anti-inflammatory drugs (NSAIDs). Higher-molecular-weight intra-articular hyaluronic acid had a greater relative effect compared with both non-selective and cyclooxygenase-2-selective oral NSAIDs. Evaluating the treatment effect estimates against a commonly utilized MCID revealed similarities in which observations attained clinical significance among treatments; however, this observation varied across the range of reported MCIDs. The present review confirmed the variability in the MCIDs for pain assessments that are used across guidelines and meta-analyses evaluating nonsurgical interventions for knee osteoarthritis. This variability may yield conflicting treatment recommendations, ranging from rejecting treatments that are indeed efficacious to accepting treatments that may not be beneficial. Additional research is required to determine why some nonsurgical therapies are more consistently recommended in knee osteoarthritis guidelines than others as these findings suggest similarities in their effect estimates for pain. Relevant stakeholders need to reach a consensus on a standard approach to determining the MCIDs for these therapies to ensure that appropriate and effective treatment options are available to patients prior to invasive surgical intervention. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies.

Topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative inflammation and pain following cataract surgery and for treatment and prophylaxis of pseudophakic cystoid macular edema (CME). Bromfenac is a brominated NSAID with strong in vitro anti-inflammatory potency. Like other ophthalmic NSAIDs, bromfenac is often used outside of the cataract surgery setting. This paper provides an overview of bromfenac’s preclinical ocular pharmacology and pharmacokinetics, followed by a review of 23 published clinical studies in which various marketed bromfenac formulations were used for conditions other than cataract surgery or pseudophakic CME. These include: post-refractive eye surgery; macular edema associated with diabetes, uveitis, or retinal vein occlusion; inflammation associated with age-related macular degeneration; pain related to intravitreal injections; and other ocular anterior segment and surface disorders with an inflammatory component. The published evidence reviewed supports the safety and effectiveness of bromfenac in these additional ophthalmic indications. Bromfenac was well tolerated when given alone or in combination with intravitreal anti-vascular endothelial growth factor agents, topical corticosteroids, or topical mast-cell stabilizers. The most common adverse event reported was ocular irritation. No serious adverse events (ie, corneal epithelial disorders) were reported, although the majority of studies did not systematically evaluate potential side effects. Corneal complications, such as melts reported with diclofenac and ketorolac, were not observed with bromfenac in the studies. In summary, published study data support the clinical utility of bromfenac in various ocular disorders beyond post-cataract surgery. Additional studies are warranted to further define the potential role of bromfenac ophthalmic solution in clinical practice.

What are the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for adults with acute pain?

What are the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for adults with acute pain?

What are the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for adults with chronic musculoskeletal pain?

What are the effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) for adults with chronic musculoskeletal pain?

Efficacy and safety of bromfenac 0.075% formulated in DuraSite for pain and inflammation in cataract surgery

ABSTRACTIntroduction: Bromfenac is a topical ophthalmic non-steroidal anti-inflammatory drug (NSAID) used to reduce pain and treat post-operative inflammation after cataract surgery. Bromfenac 0.075% in the DuraSite™ vehicle is a newly-approved formulation which has been shown to be efficacious and safe for use in cataract surgery to reduce pain and treat inflammation. It has been shown to have a slightly better posterior segment ocular bioavailability compared to similar topical ophthalmic NSAIDs. However, there is a paucity of studies investigating its role in the prevention and treatment of post-operative pseudophakic cystoid macular edema.Areas covered: In this review, the authors provide an overview of similar products available, describe the novelty of bromfenac 0.075% in the DuraSite vehicle, and discuss the relevant clinical studies to determine if the formulation is safe and efficacious.Expert opinion: Bromfenac 0.075% in the DuraSite vehicle is a new topical ophthalmic medication which has been approved by the FDA for the prevention of pain and treatment of post-operative inflammation. It provides cataract surgeons with an additional medication for cataract surgery. However, no robust studies have been performed showing the effect that it has on the reduction or prevention of post-operative pseudophakic cystoid macular edema.

OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis

To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data. We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation. Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node. These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.

SALT Trial: Steroids after Laser Trabeculoplasty: Impact of Short-Term Anti-inflammatory Treatment on Selective Laser Trabeculoplasty Efficacy

This study examined whether short-term use of topical nonsteroidal anti-inflammatory drug (NSAID) or steroid therapy affected the efficacy of selective laser trabeculoplasty (SLT). Double-masked, randomized, placebo-controlled, dual-center, multisurgeon trial. Patients older than 18 years with intraocular pressure (IOP) of more than 18 mmHg for whom the clinician decided SLT was the appropriately indicated therapy were randomized to 1 of 3 groups in a ratio of 1:1:1 as follows: ketorolac 0.5%, prednisolone 1%, or saline tears. After SLT, patients randomized into each group were instructed to use an unmarked drop 4 times daily starting the day of SLT and continuing for 4 additional days. The Kruskal-Wallis test and Wilcoxon rank-sum test were used for continuous variables when comparing 2 or 3 treatment groups, respectively. The Fisher exact test was used for categorical variables. The primary outcome of this study was IOP at 12 weeks. Secondary outcome measures included IOP at 1 and 6 weeks, patient-reported pain, and detectable anterior chamber inflammation. Ninety-six eyes of 85 patients fit inclusion criteria and were enrolled between the 2 sites. The NSAID, steroid, and placebo groups were similar in baseline demographics and baseline IOP (mean, 23.3±3.9 mmHg; P= 0.57). There was no statistically significant difference in IOP decrease among groups at week 6. Both the NSAID and steroid groups showed a statistically significantly greater decrease in IOP at week 12 compared with the placebo group (mean, -6.2±3.1 mmHg, -5.2±2.7 mmHg, and -3±4.3 mmHg, respectively; P= 0.02 [analysis of variance] and P= 0.002 [t test] for NSAID vs. placebo groups; P= 0.02 for steroid vs. placebo groups). Significantly better IOP reduction at 12 weeks was measured in eyes treated with steroid or NSAID drops after SLT. Short-term postoperative use of NSAID or steroid drops may improve IOP reduction after SLT. Longer-term follow-up studies are indicated.

Nonsteroidal antiinflammatory drugs and treatment of cystoid macular edema

Nonsteroidal antiinflammatory drugs (NSAIDs) have become a significant therapeutic adjunctive tool in the routine and complicated intraocular surgery. Topical NSAIDs prevent intraoperative miosis, reduce pain, postoperative inflammation and incidence of cystoid macular edema (CME). Although there is no established protocol for prophylaxis of pseudophakic CME, due to the relationship between proinflammatory prostaglandins and CME, using corticosteroids and NSAIDs could prevent CME. NSAIDs have a synergistic antiinflammatory effect with steroids, but can also be used alone when corticosteroid therapy could be harmful. Prospective clinical trials need to define treatment protocol for topical NSAIDs use, due to their powerful influence to prevent perioperative complications.

New progress of diagnosis and treatment in pseudophakic cystoid macular edema

Pseudophakic cystoid macular edema (PCME) is one of the most common complications of cataract surgery.It is the main cause of postoperative visual loss.PCME pathogenesis is unclear yet, inflammation is supposed to be an important cause.Systemic or local diseases, and complicated surgical operations may increase the risk of PCME.Diabetes is the most common independent risk factor, and the risk of PCME is closely related to severity of preoperative diabetes.Typical clinical symptoms of PCME include acute vision loss after surgery.In PCME eyes, fundus fluorescein angiography (FFA) can show the petal-like spots characteristically, and visual disc dot staining can be seen later.Cystoid macular edema (CME) first appears in the inner nuclear layer (INL) and gradually develops in the outer plexiform layer (OPL). Finally, fluid accumulates in the subretinal space.Besides, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have new advances in differential diagnosis between PCME and diabetic macular edema (DME). In practice, topical non-steroid anti-inflammatory drugs (NSAIDs) or glucocorticoids are generally used as first-line treatment medicines.Anti-vascular endothelial growth factor (anti-VEGF) also attracts attention as a new treatment.Individualized prevention and treatment is required for specific types of PCME.It still lacks a common recognized treatment of PCME, and long-term efficacy of the current treatment remains to be observed more rigorous and comprehensive experimental programs are required. Key words: Pseudophakic cystoid macular edema; Diabetic macular edema; Optical coherence tomography angiography; Anti-vascular endothelial growth factor; Femtosecond laser assisted

Safety of Topical Non-steroidal Anti-Inflammatory Drugs in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

ObjectiveWe aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.MethodsA comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.ResultsThe search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04–1.29; I2 = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15–1.92; I2 = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96–3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73–1.27).ConclusionsTopical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.Electronic supplementary materialThe online version of this article (10.1007/s40266-019-00661-0) contains supplementary material, which is available to authorized users.

Importance of the formulation in the skin delivery of topical diclofenac: not all topical diclofenac formulations are the same.

Purpose: The current study aimed to compare 2 topical diclofenac products (diclofenac diethylamine [DEA] 1.16% emulsion and diclofenac sodium [Na] 5% gel). The quantitative evaluation of skin permeability and the qualitative evaluation of their physical characteristics were performed.Methods: The skin permeability of diclofenac DEA 1.16% emulsion and diclofenac Na 5% gel was compared in vitro using Franz diffusion cells following a single, fixed, 10 mg/cm2 dose of product applied to a 0.64 cm2 area of the stratum corneum surface of ex vivo human skin samples. The physical characteristics of the 2 formulations were assessed by rheological measurement and microscopy observation.Results: Diclofenac DEA 1.16% emulsion exhibited a statistically significant higher permeation through human skin at 24 hrs than diclofenac Na 5% gel (554 vs 361 ng/cm2, respectively; ratio of adjusted geometric means, 1.54 [95% CI, 1.14–2.07]). When expressed as a percentage of the applied dose of diclofenac that permeated through human skin, a 7-fold difference was observed between the diclofenac DEA 1.16% emulsion (0.54%) and the diclofenac Na 5% gel (0.077%). Qualitative composition and physical characterization showed differences between the formulations that may explain some of the permeation data observed. Based on rheological assessments, diclofenac Na 5% gel had a higher viscosity (24.82 Pa.s) than diclofenac DEA 1.16% emulsion (10.29 Pa.s).Conclusion: A topical diclofenac product with a higher concentration of the active ingredient does not necessarily lead to greater absorption relative to a product with lower concentration of the active ingredient but different characteristics. These observations highlight the importance of considering parameters beyond drug concentration, such as composition, which may influence the solubility of the drug and permeation of topical nonsteroidal anti-inflammatory drugs.

The Role of Steroids and NSAIDs in Prevention and Treatment of Postsurgical Cystoid Macular Edema.

Pseudophakic cystoid macular edema (PCME) remains one of the most common visionthreatening complication of phacoemulsification cataract surgery (PCS). Pharmacological therapy is the current mainstay of both prophylaxis, and treatment of PCME in patients undergoing PCS. We aimed to review pharmacological treatment options for PCME, which primarily include topical steroids, topical nonsteroidal antiinflammatory drugs (NSAIDS), periocular and intravitreal steroids, as well as anti-vascular endothelial growth factor therapy. The PubMed and Web Of Science web platforms were used to find relevant studies using the following keywords: cataract surgery, phacoemulsification, cystoid macular edema, and pseudophakic cystoid macular edema. Of articles retrieved by this method, all publications in English and abstracts of non-English publications were reviewed. Other studies were also considered as a potential source of information when referenced in relevant articles. The search revealed 193 publications. Finally 82 articles dated from 1974 to 2018 were assessed as significant and analyzed. Based on the current literature, we found that corticosteroids remain the mainstay of PCME prophylaxis in uncomplicated cataract surgery, while it is still unclear if NSAID can offer additional benefits. In patients at risk for PCME development, periocular subconjunctival injection of triamcinolone acetonide may prevent PCME development. For PCME treatment the authors recommend a stepwise therapy: initial topical steroids and adjuvant NSAIDs, followed by additional posterior sub-Tenon or retrobulbar corticosteroids in moderate PCME, and intravitreal corticosteroids in recalcitrant PCME. Intravitreal anti-vascular endothelial growth factor agents may be considered in patients unresponsive to steroid therapy at risk of elevated intraocular pressure, and with comorbid macular disease. Therapy with topical corticosteroids and NSAIDs is the mainstay of PCME prophylaxis and treatment, however, periocular and intravitreal steroids should be considered in refractory cases.