Open access Original research BMJ Open: first published as 10.1136/bmjopen-2018-026752 on 2 November 2019. Downloaded from Difluprednate versus Prednisolone Acetate after Cataract Surgery: a Systematic Review and Meta- Analysis Mahmoud Tawfik KhalafAllah , Ahmed Basiony, Ahmed Salama To cite: KhalafAllah MT, ABSTRACT Strengths and limitations of this study Basiony A, Salama A. Objective Topical steroids are the cornerstone in Difluprednate versus controlling the inflammation after cataract surgery. ► This is the first systematic review to summarize the Prednisolone Acetate Prednisolone acetate and difluprednate are the two main after Cataract Surgery: a evidence for topical steroids after cataract surgery products for this purpose. However, it is unclear which one Systematic Review and in terms of effectiveness and safety. should be used in terms of effectiveness and safety. Meta- Analysis. BMJ Open ► The comprehensive search of the databases (yield- Design Systematic review and meta- analysis. 2019;9:e026752. doi:10.1136/ ing three trials) and the hand searching (yielding Data sources Medline via PubMed, Cochrane Central bmjopen-2018-026752 three additional trials) provide a holistic approach Register of Controlled Trials, Web of science and for this question. ► Prepublication history and clinicaltrials.gov were searched through 10 January 2018, additional material for this ► The Grading of Recommendations Assessment, and updated on 20 July 2019, in addition to researching paper are available online. To Development, and Evaluation approach is applied the references’ lists of the relevant articles. view these files, please visit aiming to evaluate the certainty of the synthesised Eligibility criteria Randomised-controlled trials (RCTs) the journal online (http:// dx. doi. evidence to help clinicians make better decisions. org/ 10. 1136/ bmjopen- 2018- comparing difluprednate and prednisolone acetate ► The main limitation is the inherent bias and hetero- regardless of the dosing regimen used. 026752). geneity in the included studies. Data extraction and synthesis Two independent authors ► The subgroup analysis for the age and technique Received 29 September 2018 assessed the included RCTs regarding the risk of bias can alleviate that limitation. Revised 13 September 2019 using the Cochrane tool. Relevant data were extracted, Accepted 27 September 2019 and meta-analysis was conducted using a random-effects model. The Grading of Recommendations Assessment, about eight million cataract surgeries are Development, and Evaluation approach was used to appraise the evidence quality. performed annually. Moreover, increased life Results We included six RCTs with 883 patients: 441 expectancy justifies the expectation that even http://bmjopen.bmj.com/ received difluprednate and 442 received prednisolone more surgeries will be performed in the next 1 acetate. The evidence quality was graded as moderate years. Fortunately, cataract surgery is among for corneal oedema and intraocular pressure and low the most successful procedures, in particular for anterior chamber (AC) clearance. After small incision the phacoemulsification or the small incision cataract surgery, difluprednate was superior in clearing cataract surgery (SICS) techniques. Tech- AC cells at 1 week (OR=2.5, p>0.00001) and at 2 weeks nological advances in this field have led to (OR=2.5, p=0.04), as well as clearing the AC flare at higher patient expectations regarding visual 2 weeks (OR=6.7, p=0.04). After phacoemulsification, 2 outcomes and comfort of the procedure. on September 30, 2021 by guest. Protected copyright. difluprednate was superior in terms of corneal clarity Postoperative inflammation is a commonly at 1 day (OR=2.6, p=0.02) and 1 week after surgery (OR=1.96, p=0.0007). No statistically significant difference encountered event after cataract surgery. In was detected between both agents at 1 month in most cases it is low grade and self- limiting, effectiveness. Also, both agents were safe, evaluated by with slight patient's discomfort, which may 3 © Author(s) (or their the ocular hypertension (OR=1.23, p=0.8). persist for days after the surgery. Neverthe- employer(s)) 2019. Re- use Conclusion With low-to- modera te certainty, difluprednate less, suboptimal vision is a rare, yet signifi- permitted under CC BY-NC. No and prednisolone acetate are safe agents for controlling cant consequence of severe inflammation. commercial re- use. See rights the inflammation after cataract surgery. Difluprednate Corneal oedema, secondary glaucoma, and permissions. Published by showed significant superiority in terms of AC cells and AC BMJ. anterior or posterior synechia and macular flare at 2 weeks postoperatively. Ophthalmology Department, oedema are reported events related to severe Menoufia University Faculty inflammation. Thus, adequate management 4 of Medicine, Shebin El- Kom, of postcataract inflammation is essential. Menoufia, Egypt INTRODUCTION Although different anti- inflammatory agents Cataract is the leading cause of blindness are available, those with corticosteroids are Correspondence to 5 Dr Mahmoud Tawfik KhalafAllah; worldwide, mainly affecting the elderly the most common. mahmoud. tawfik@ med.menofia. population. Presently, surgery is the only Corticosteroids are potent inhibitors of edu. eg therapeutic option for cataracts. That is why phospholipase A2 enzyme, which control KhalafAllah MT, et al. BMJ Open 2019;9:e026752. doi:10.1136/bmjopen-2018-026752 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-026752 on 2 November 2019. Downloaded from synthesis of arachidonic acid, the precursor of many and thereby its potency, compared with all other steroid inflammatory mediators. That is how corticosteroids can molecules. Moreover, difluprednate has enhanced pene- suppress the inflammatory response and guard against tration to the uvea, due to the acetate ester group at C21. complications. However, side effects are a major source of Since 2008, many studies have investigated the safety and concern when using treatments containing these agents. effectiveness of the new drug, which has shown encour- Impaired healing and ocular hypertension are not rare aging results, with growing use in clinical practice, along- events associated with corticosteroid use.6 Different side prednisolone.9 agents are available, and prednisolone acetate is the Many randomised- controlled trials (RCTs) were most widely prescribed. Prednisolone acetate has broad conducted to compare both agents in real-life settings and potent anti- inflammatory effects, which have been after cataract surgery. However, no quantitative evidence reported for decades. Being lipophilic, it is available in exists. In this review, we aim to compare the two major a suspension form that requires shaking before admin- anti- inflammatory agents: prednisolone acetate and istration. With low patient compliance, dose uniformity difluprednate after cataract surgery using either the is a great concern.7 To overcome this, some physicians phacoemulsification method or the SICS method. Such practice more frequent dosing of prednisolone, which comparison will help elucidate the safety and effective- in turn increases the risk of the previously reported ness of both agents after routine cataract surgery. complications. In 2008, the Food and Drug Administration (FDA) approved the use of difluprednate to control pain and inflammation after ocular surgery.8 Difluprednate is a METHODS butyrate ester derivative of prednisolone, with two fluo- Eligibility criteria for considering studies for this review rine atoms at C6 and C9. As an emulsion, difluprednate Types of studies drops provide consistent and uniform doses without We considered RCTs in which difluprednate was compared requiring shaking.7 In addition, the difluorination of the with prednisolone acetate regardless of the dosing molecule increases its affinity to glucocorticoid receptors, regimen used. Given that it is a recent clinical question http://bmjopen.bmj.com/ on September 30, 2021 by guest. Protected copyright. Figure 1 Preferred reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) flow diagram. 2 KhalafAllah MT, et al. BMJ Open 2019;9:e026752. doi:10.1136/bmjopen-2018-026752 Open access BMJ Open: first published as 10.1136/bmjopen-2018-026752 on 2 November 2019. Downloaded from with few RCTs conducted to date, quasi- randomised trials Types of outcome measures as well as conference abstracts were considered. RCTs were considered if at least one of the following outcomes was reported: Types of participants We included trials in which participants underwent Primary outcome measures uncomplicated cataract surgery with or without intraoc- 1. The effectiveness of the drug, indicated by the propor- ular lens (IOL) implantation. To be included, partici- tion of participants with no cell or flare at day 15 (±2 pants must be free from any ocular or systemic disease days). that could flare or suppress the inflammatory response, 2. The safety of the drug, indicated by the proportion including but not limited to diabetes mellitus, uveitis and of participants who experienced intraocular pressure systemic immunological diseases. Either phacoemulsifica- (IOP) elevations. tion or SICS procedures were eligible. No age restrictions Secondary outcome measures were applied. 1. Other effectiveness measures: absence of anterior chamber (AC) cells or flare at days 1, 7 (±1 day) and Patient and public involvement 28 (±2 days), and absence of corneal oedema