Corticosteroids for periorbital and orbital cellulitis

Abstract

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

To assess the effectiveness and safety of adjunctive corticosteroids for periorbital and orbital cellulitis, and assess their effectiveness and safety in children and in adults separately.

Background

Description of the condition

Although periorbital (preseptal) and orbital (postseptal) cellulitis are anatomically distinct bacterial infections, clinical differentiation is often difficult, and these two conditions usually are considered together (Wong 2018). Periorbital cellulitis is an infection of the tissues anterior to the orbital septum, caused by spread of a local infection such as conjunctivitis, or following injury (Rimon 2008). Orbital cellulitis is an infection of the tissues posterior to the orbital septum, usually as a complication of sinusitis (Howe 2004). In both conditions, people present with periorbital swelling and redness. Swelling may be severe making exam of the eye challenging. Orbital cellulitis is characterized by decreased ocular movement, pain with eye movements, decreased visual acuity, and proptosis, whereas these clinical features are absent in periorbital cellulitis. In 1970, Chandler and colleagues described criteria for categorizing severity (Chandler 1970). Periorbital cellulitis (Chandler criteria I) is defined as an infection of the eye lid, or tissue around the eye; orbital cellulitis (Chandler criteria II) is defined as an infection of the structures posterior to orbital septum; orbital cellulitis is further categorized according to presence of subperiosteal abscess (Chandler criteria III), orbital abscess (Chandler criteria IV), and cavernous sinus thrombosis (Chandler criteria V). Severe complications of orbital cellulitis include loss of vision, meningitis, and death (Crosbie 2016; Lee 2011; Murphy 2014).

The incidence of orbital cellulitis is estimated to range from 1.6 per 100,000 to 6 per 100,000 in children under the age of 18 years, and 0.6 per 100,000 to 2.4 per 100,000 in adults, although few published studies have evaluated incidence (Capra 2015; Murphy 2014; Soroudi 2003). Children under the age of 18 years represent a large proportion of people hospitalized with orbital cellulitis (Marchiano 2016). Based on the US Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample, which uses weighted national estimates, there were approximately 6400 hospitalizations in 2013 across all ages, and approximately 2500 hospitalizations in children (HCUPnet). Across all ages, the estimated cost of these hospitalizations was over USD 41 million per year, the mean age was 33 years, there was a slight male predominance at 52%, and the mean length of stay was four days (HCUPnet). One US study compared outcomes of children hospitalized with orbital cellulitis in 2000 (prior to the introduction of the heptavalent pneumococcal vaccine) to 2009 and reported that surgical rates nearly doubled and hospital charges more than doubled (Capra 2015).

Microbiologic isolates have changed over the decades. Haemophilus influenzae type B was the most common pathogen prior to the introduction of the vaccine (1985), after which Streptococcus pneumoniae predominated (Donahue 1998; Harris 1994). Peña and colleagues examined sinus and blood cultures of children with orbital cellulitis at one US children's hospital in two eras, pre‐ and postintroduction of the 7‐valent pneumococcal conjugate vaccine (2003) (Pena 2013). Prior to the introduction of the vaccine, Spneumoniae was the predominate pathogen, but was not found in any children postvaccine (from 22% to 0%). There was a similar reduction inStreptococcus viridans (from 12% to 0%). There was an increase in Staphylococcus aureus (from 20% to 42%) and of those, there was methicillin‐resistance only in the postvaccine era (from 0% to 56%). However, in one study from Toronto, Canada (2000 to 2011), of those children with a positive culture, 13.3% grew H influenzae from their abscess drainage, leading the authors to conclude that this pathogen remains a cause of orbital cellulitis, especially in older children with larger abscesses (Sharma 2015).

The indications for computer tomography (CT) imaging have been examined, and are especially important considering the risks to young children from exposure to ionizing radiation. Rudloe and colleagues examined the charts of children attending a US pediatric emergency department (1995 to 2008) presenting with acute periorbital edema or erythema, or both (Rudloe 2010). Of these, 32% underwent CT imaging; 12% of all children and 37% of those with CT scans had significant CT findings (defined as Chandler III or higher), of which 91% were Chandler III (subperiosteal abscess). Children reporting pain on eye movement or having proptosis or ophthalmoplegia at clinical exam had increased risk of having an orbital abscess at CT. Authors of one systematic review concluded that periorbital and orbital cellulitis can be managed medically; subperiosteal abscess often can be managed medically; and orbital abscess and cavernous sinus thrombosis are managed surgically (Wong 2018). Surgical management also is indicated for people who fail to respond to antimicrobial therapy, or complications develop (e.g. optic nerve compromise). Studies have shown similar efficacy of oral and parenteral antibiotics for uncomplicated periorbital cellulitis (Al‐Nammari 2007), while intravenous (IV) antibiotics are warranted for orbital cellulitis, subperiosteal abscess, and orbital abscess (Wong 2018).

Description of the intervention

A small number of studies have suggested that adding corticosteroids to antimicrobial therapy may improve outcomes in people with periorbital and orbital cellulitis (Chen 2018; Davies 2015; Pushker 2013; Yen 2005). Two prospective, comparative observational studies that evaluated the effectiveness of corticosteroids in children hospitalized with orbital cellulitis noted a three‐day reduction in length of stay (Chen 2018; Davies 2015). One randomized controlled trial (RCT) of 21 people aged over 10 years of age with orbital cellulitis admitted to a tertiary care eye hospital in India reported that people treated with corticosteroids, had a three‐day reduction in duration of IV antibiotics and a four‐day reduction in mean length of stay with no difference in observed need for surgical intervention (Pushker 2013). Further, people treated with corticosteroids had less pain, periorbital edema, fever, and chemosis. At 12 weeks' follow‐up, people treated with corticosteroids had less residual proptosis and restrictions in extraocular movement, and no adverse effects. However, there are no clinical practice guidelines to guide practitioners on the use of corticosteroids in people with periorbital and orbital cellulitis.

How the intervention might work

Orbital cellulitis causes inflammation and swelling leading to a compartment syndrome within the enclosed bony orbit, resulting in elevated ocular pressure and compression of the vasculature, musculature, and optic nerve, resulting in ischemia, ophthalmoplegia, and visual impairment respectively. Corticosteroids have several beneficial effects when used for acute illness, including reducing inflammation and edema, and are used for several other infections to reduce inflammation and swelling. For example, corticosteroids are standard of care for children with mild, moderate, and severe croup, a viral infection of the larynx and trachea, leading to a reduced frequency of hospitalization, and intensive care unit admission (Gates 2018). There is clinical precedence for the use of corticosteroids in several other acute infections, including bacterial meningitis (Brouwer 2015), tuberculosis meningitis (Prasad 2016), bacterial meningitis in neonates (Ogunlesi 2015), and acute bacterial sinusitis (Venekamp 2014). Some authors have reported clinical reticence to use corticosteroids due to concerns with immune suppression and fear of worsening infection (Chen 2018; Davies 2015), although studies have not supported these assertions.

Why it is important to do this review

The results of studies to date have been inconclusive on the use of corticosteroids in people with periorbital and orbital cellulitis. One large US‐based multi‐center observational study identified significant variation in the use of adjunctive corticosteroids for children hospitalized with periorbital and orbital cellulitis, highlighting an important evidence gap (Markham 2018). Questions remain on the type of corticosteroids (e.g. dexamethasone, prednisolone), dose, route (IV versus oral versus intranasal), duration, timing (before, during, or after antibiotics or when responding to therapy), and indication (periorbital cellulitis versus orbital cellulitis versus subperiosteal/orbital abscess). No prior systematic review has evaluated whether adjunctive corticosteroids improve outcomes. A synthesized body of evidence is necessary to optimize outcomes for people with periorbital and orbital cellulitis.

Objectives

To assess the effectiveness and safety of adjunctive corticosteroids for periorbital and orbital cellulitis, and assess their effectiveness and safety in children and in adults separately.

Methods

Criteria for considering studies for this review

Types of studies

We will include RCTs, with and without treatment masking, and quasi‐RCTs (i.e. controlled clinical trials). Studies will be included independently of the language of publication, publication status (unpublished, published), sample size or risk of bias. There will be no minimum follow‐up period for trial eligibility.

Types of participants

We will include studies that enrolled participants of any age with clinically diagnosed periorbital and orbital cellulitis, including all ranges of severity as defined by Chandler (Chandler 1970). We will include studies that enrolled participants who were clinically diagnosed with periorbital or orbital cellulitis, irrespective of whether radiographic imaging was completed. We will include studies conducted in both inpatient and outpatient settings (e.g. emergency room, ambulatory care, outpatient clinic).

We will exclude studies that focus exclusively on participants who were undergoing elective endoscopic surgery, including management of infections postsurgery. We will exclude studies conducted solely on trauma patients.

Types of interventions

We will include studies that focused on the short‐term use of adjunctive systemic corticosteroids (e.g. dexamethasone, prednisone, prednisolone, methylprednisolone) or intranasal corticosteroids (e.g. fluticasone, betamethasone) administered for the acute care of people with periorbital and orbital cellulitis. We will consider all types of corticosteroids, dose, mode of delivery (i.e. oral, IV, or intranasal), length of therapy, or timing of treatment (i.e. prior to or at the time of antibiotic administration, or delayed). We will include comparators that are placebo, another corticosteroid, no treatment control, or another intervention.

Types of outcome measures

There is no core outcome set for periorbital or orbital cellulitis on which to base outcome selection.

The critical outcomes of this review will include:

• Time to recovery. If this is not reported, we will consider mean length of hospital stay (hours or days) for studies focused on hospitalized participants as a surrogate to time to recovery.

• Proportion of participants recovered at the end of follow‐up, as defined by each individual study.

• Proportion of participants with preservation of visual acuity at the end of the study intervention period, defined as not worsening from baseline measure of best corrected visual acuity (BCVA) on a standardized age‐appropriate assessment tool (e.g. logMAR values, Snellen chart).

• Severity of pain as reported by participant or caregiver as defined using mean difference on a standard age‐appropriate assessment tool (e.g. visual analog score) from baseline and throughout the study period (duration of hospitalization for inpatients, or until resolution of symptoms for outpatients) at day 1, day 2, day 3, day 7, day 10 and day 14. We chose multiple time points for this outcome because hospitalized participants with orbital cellulitis are frequently assessed daily, which results in management decisions (e.g. surgical intervention). Therefore, these time points are clinically meaningful for treatment decisions, and meaningful to families (i.e. pain improving or worsening). Prior studies on corticosteroids in hospitalized participants identified clinical differences at these time points.

• Mean duration of time (hours or days) requiring IV antibiotics during study period.

• Proportion of participants who required surgical intervention during study period.

• Adverse effects associated with corticosteroids, including behavioral problems, hyperactivity, gastric irritation, hyperglycemia, adrenal suppression, weight gain, cataracts, and immune suppression. We will document other adverse events reported from trials.

Other important outcomes of this review will include:

• Proportion of participants with normal extraocular muscle movement at the end of the study intervention period, defined using an objective tool (e.g. Kestenbaum limbus test of motility) or at clinical exam and in the absence of any reported diplopia.

• Proportion of participants who had a return visit to healthcare provider during the first 7 days and between 7 and 30 days after the end of the study.

• Proportion of participants who died at the end of follow‐up.

We will not conduct a formal cost‐effectiveness analysis, but when data are available, we will compare costs associated with and without steroid use.

Search methods for identification of studies

Electronic searches

The Cochrane Eyes and Vision Information Specialist will search the following electronic databases for RCTs and controlled clinical trials. There will be no restrictions to language or year of publication.

• Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (latest issue) (Appendix 1).

• MEDLINE Ovid (1946 to present) (Appendix 2).

• Embase.com (1947 to present) (Appendix 3).

• PubMed (1948 to present) (Appendix 4).

• LILACS (Latin American and Caribbean Health Science Information Database (1982 to present) (Appendix 5).

• US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 6).

• World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp) (Appendix 7).

Searching other resources

We will search conference proceedings for abstracts that describe potentially relevant trials. We will identify additional published, unpublished, or ongoing studies by handsearching reference lists of relevant articles, included and excluded articles (backward searching), using the Science Citation Index for papers cited (forward searching), and by contacting topic experts in the field (hospital‐based pediatricians, pediatric emergency physicians, ophthalmologists, and otolaryngologists).

Data collection and analysis

Selection of studies

Two review authors will independently screen all titles, abstracts, and keywords (when available) generated by the electronic searches for inclusion, and each record will be classified as 'definitely relevant', 'possibly relevant', or 'definitely not relevant'. We will obtain the full text of all studies reported in articles classified as 'definitely relevant' or 'possibly relevant' to review and determine whether the study meets the inclusion criteria. Two review authors will independently review each full‐text report, and classify the study reported as 'include', 'exclude', or 'unsure'. All disagreements will be resolved by discussion and consensus; a third review author will be consulted whenever necessary. For articles excluded after full‐text review, we will document reasons for exclusion in the 'Characteristics of excluded studies' table. The search and selection process will be described in a PRISMA flow diagram (Moher 2009).

Where studies have multiple publications, we will collate the reports of the same study so that each study, rather than each report, is the unit of interest for the review, and such studies have a single identifier with multiple references.

Data extraction and management

We will adapt a data collection form developed and piloted by Cochrane Eyes and Vision. Two review authors will independently extract study information; any disagreements will be resolved by discussion and consensus. When necessary a third review author will reach a final decision. The data extraction form will include details related to the trial methodology, characteristics of the participants, interventions, outcomes, and additional information (e.g. funding, conflicts of interests, trial registration). We will complete a 'Characteristics of included studies' table; One review author will transfer data into Review Manager 5 (Review Manager 2014), and a second review author will verify that data were entered correctly.

Assessment of risk of bias in included studies

We will assess risk of bias in the included studies using Cochrane's domain‐based evaluation tool as recommended in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2019). We will use the Cochrane 'Risk of bias' tool to assess the following domains of bias: selection bias (random sequence generation, allocation concealment before randomization), performance bias (masking of participants and personnel), detection bias (masking of outcome assessment), attrition bias (incomplete outcome data, amount, and handling of missing data), reporting bias (selective outcome reporting), and other sources of bias (e.g. funding source). Two review authors will independently assess risk of bias for each domain ('low risk', 'unclear risk', or 'high risk') and resolve discrepancies by discussion; a third review author will be consulted whenever necessary to make a final judgment. We will contact trial authors and wait for two weeks if there is uncertainty in any domain due to lack of information.

Measures of treatment effect

We will analyze dichotomous data using risk ratio with 95% confidence intervals (CIs). Dichotomous outcomes include patient recovery at the end of follow‐up period, preservation of visual acuity, normal extraocular movements, surgical intervention, adverse events, return visit to a healthcare provider, and death.

We will analyze continuous data as mean difference with 95% CIs when measurements were made using the same scale, or standardized mean differences with 95% CIs when measurements were made using different scales. Continuous outcomes include time to recovery, length of hospital stay, severity of pain, and duration of antibiotics.

Unit of analysis issues

The unit of analysis will be the participant. The treatments that we are evaluating are systemic, therefore will affect both eyes equally. When trials with more than two arms are included (e.g. two or more doses), we will evaluate each relevant comparison separately without double counting them in the analysis.

Dealing with missing data

We will contact investigators to obtain missing information, either for a study that has been reported in an abstract only, or when insufficient detail is provided in full‐text reports. If the study investigators do not respond within two weeks, we will proceed with available information and evaluate the impact of the missing data on the overall assessment of results. We will use recommended guidelines in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions to manage potentially missing data (Higgins 2011a).

Assessment of heterogeneity

We will assess clinical heterogeneity by comparing the characteristics of individual studies (i.e. study participants, inclusion/exclusion criteria and outcomes). We will assess methodologic heterogeneity by comparing design characteristics, including risk of bias assessment of individual studies. We will use the I² statistic to assess statistical heterogeneity in the outcome estimates from included studies (Higgins 2011b). If we detect significant, clinical, methodologic, or statistical heterogeneity (defined as I² statistic above 60%), we will explore reasons for heterogeneity and may decide not to combine data in a meta‐analysis.

Assessment of reporting biases

We will attempt to mitigate reporting biases by searching the grey literature for unpublished studies. If 10 or more studies are included, we will assess small‐study effect, which could be due to publication bias using funnel plots.

Data synthesis

We will synthesize the data qualitatively, focusing on the comparability of studies and characteristics of studies that may affect the cumulative evidence. We will undertake a meta‐analysis, when deemed appropriate, using a random‐effects model due to expected variation that will be observed between studies.

Subgroup analysis and investigation of heterogeneity

If sufficient data are available, we will conduct several subgroup analyses of outcomes, according to:

• age: children (aged 18 years and under) versus adults (aged over 18 years);

• route of corticosteroids: systemic (oral, IV) versus intranasal;

• timing of corticosteroids: immediately at diagnosis versus delayed to when responding to therapy;

• setting: inpatient versus outpatient.

We anticipate finding few studies, and that analysis of outcomes within these subgroups may not be possible. If subgroup analyses are performed, we will use the recommended subgroup interactions test (Chi² test; Higgins 2011b).

Sensitivity analysis

We will conduct the following sensitivity analyses if sufficient number of studies are available:

• effect of excluding studies with a high risk of bias for the primary outcome on any domain;

• effect of excluding unpublished data (if relevant).

'Summary of findings' table

We will present a 'Summary of findings' table for each comparison when data are available. The comparison will be adjunctive systemic or intranasal corticosteroids versus control, or another comparator. We will include the following seven outcomes at the end of the study period.

• Time to recover, or mean length of hospital stay.

• Proportion of participants with preservation of visual acuity at the end of the study period.

• Severity of pain as reported by participant or caregiver on day three.

• Mean duration of time requiring antibiotics.

• Proportion of participants who required surgical intervention.

• Adverse effects associated with corticosteroids.

• Proportion of participants who had a return visit to healthcare at the end of the study period.

We will assess the quality of a body of evidence in relation to each prespecified outcome using the core GRADE components: study limitations, consistency of effect, imprecision, indirectness, and publication bias. We will use GRADEprofile software to assist in preparing the 'Summary of Findings' tables (GRADEpro GDT). We will detail the reasons why the evidence is either upgraded or downgraded.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Cellulitis] explode all trees
 #2 MeSH descriptor: [Orbital Cellulitis] explode all trees
 #3 ((periorbit* OR orbit* OR preseptal OR "pre septal" OR postseptal OR "post septal") NEAR/3 celluliti*)
 #4 ((subperiosteal OR "sub periosteal" OR orbital OR intraconal) NEXT/1 abscess*)
 #5 MeSH descriptor: [Eye Infections, Bacterial] explode all trees
 #6 (Bacterial NEAR/3 eye infect*)
 #7 MeSH descriptor: [Orbital Diseases] this term only
 #8 orbital NEXT/1 disease*
 #9 MeSH descriptor: [Sinusitis] explode all trees
 #10 sinusitis OR (sinus NEXT/2 infect*) OR rhinosinusitis
 #11 "Sinus venous thrombosis"
 #12 {OR #1‐#11}
 #13 MeSH descriptor: [Orbital Cellulitis] explode all trees and with qualifier(s): [drug therapy ‐ DT]
 #14 MeSH descriptor: [Steroids] explode all trees
 #15 Steroid*
 #16 MeSH descriptor: [Adrenal Cortex Hormones] explode all trees
 #17 (("Adrenal Cortex" NEXT/1 Hormone*) OR Corticosteroid* OR Corticoid* OR Glucocorticoid* OR (Glucorticoid NEXT/1 Effect*) OR Hydroxycorticosteroid* OR ("Adrenal cortical" NEXT/1 hormone*) OR (Adrenocortical NEXT/1 hormone*) OR Adrenocorticosteroid* OR Dermocorticosteroid*)
 #18 Glucocorticosteroid* OR Glucocorticoidsteroid* OR Glucocortoid* OR Glycocorticoid* OR Glycocorticosteroid*
 #19 Dexamethasone OR adrecort OR adrenocot OR "aeroseb dex" OR aflucoson OR aflucosone OR alfalyl OR anaflogistico OR arcodexan OR arcodexane OR artrosone OR azium OR bidexol OR calonat OR cebedex OR cetadexon OR colofoam OR corsona OR cortastat OR cortidex OR cortidexason OR cortidrona OR cortidrone OR cortisumman OR "dacortina fuerte" OR "dacortine fuerte" OR dalalone OR danasone OR "de‐sone la" OR decacortin OR decadeltosona OR decadeltosone OR decaderm OR decadion OR decadran OR decadron OR decadronal OR decadrone OR decaesadril OR decaject OR decameth OR decamethasone OR decasone OR decaspray OR decasterolone OR decdan OR decilone OR decofluor OR dectancyl OR dekacort OR delladec OR deltafluoren OR deltafluorene OR dergramin OR deronil OR desacort OR desacortone OR desadrene OR desalark OR desameton OR desametone OR desigdron OR "dexa cortisyl" OR "dexa dabrosan" OR "dexa korti" OR "dexa scherosan" OR "dexa scherozon" OR "dexa scherozone" OR "dexa‐p" OR "dexacen 4" OR dexachel OR dexacort OR dexacortal OR dexacorten OR dexacortin OR dexacortisyl OR dexadabroson OR dexadecadrol OR dexadrol OR dexagel OR dexagen OR dexahelvacort OR dexakorti OR dexalien OR dexalocal OR dexame OR dexamecortin OR dexameson OR dexamesone OR dexametason OR dexametasone OR dexameth OR dexamethason OR dexamethazon OR dexamethonium OR dexamonozon OR dexan OR dexane OR dexano OR dexapot OR dexascheroson OR dexascherozon OR dexascherozone OR dexason OR dexasone OR dexinoral OR dexionil OR dexmethsone OR dexona OR dexone OR dexpak OR dextelan OR dextrasone OR dexycu OR dezone OR dibasona OR doxamethasone OR esacortene OR "ex s1" OR exadion OR exadione OR firmalone OR "fluormethyl prednisolone" OR fluormethylprednisolon OR fluormethylprednisolone OR fluormone OR fluorocort OR fluorodelta OR fluoromethylprednisolone OR fortecortin OR gammacorten OR gammacortene OR grosodexon OR grosodexone OR hexadecadiol OR hexadecadrol OR hexadiol OR hexadrol OR isnacort OR "isopto dex" OR "isopto maxidex" OR "isopto‐maxidex" OR isoptodex OR isoptomaxidex OR "lokalison f" OR loverine OR luxazone OR marvidione OR maxidex OR mediamethasone OR megacortin OR mephameson OR mephamesone OR metasolon OR metasolone OR "methazon ion" OR "methazone ion" OR methazonion OR methazonione OR methylfluorprednisolone OR "metisone lafi" OR mexasone OR millicorten OR millicortenol OR "mk 125" OR mk125 OR mymethasone OR neoforderx OR neofordex OR nisomethasona OR novocort OR "nsc 34521" OR nsc34521 OR "oftan‐dexa" OR opticorten OR opticortinol OR oradexan OR oradexon OR oradexone OR orgadrone OR ozurdex OR pidexon OR policort OR posurdex OR "predni f tablinen" OR "predni‐f" OR "prednisolone f" OR prodexona OR prodexone OR sanamethasone OR santenson OR santeson OR sawasone OR solurex OR spoloven OR sterasone OR thilodexine OR triamcimetil OR vexamet OR visumetazone OR visumethazone OR "50‐02‐2"
 #20 Prednisone OR ancortone OR biocortone OR colisone OR cortan OR cortancyl OR cortidelt OR cortiprex OR cutason OR dacorten OR "de cortisyl" OR decortancyl OR dacortin OR decortin OR decortine OR decortisyl OR dehydrocortisone OR dekortin OR delitisone OR "dellacort a" OR "delta cortelan" OR "delta cortisone" OR "delta dome" OR "delta e" OR "delta prenovis" OR deltacorten OR deltacortene OR deltacortisone OR deltacortone OR deltasone OR deltison OR deltisona OR deltra OR "di adreson" OR diadreson OR drazone OR encorton OR encortone OR enkorton OR enkortolon OR fernisone OR hostacortin OR insone OR "liquid pred" OR lodotra OR "me‐korti" OR meprison OR metacortandracin OR meticorten OR meticortine OR nisona OR "nsc 10023" OR nsc10023 OR orasone OR orisane OR panafcort OR panasol OR paracort OR pehacort OR precort OR precortal OR "predni tablinen" OR "prednicen‐m" OR prednicorm OR prednicot OR prednidib OR predniment OR prednison OR prednitone OR "pregna 1, 4 diene 3, 11, 20 trione 17, 21 diol" OR pronison OR pronisone OR pronizone OR pulmison OR rayos OR rectodelt OR servisone OR sone OR steerometz OR sterapred OR ultracorten OR urtilone OR winpred OR "53‐03‐2"
 #21 Prednisolone OR adelcort OR antisolon OR antisolone OR aprednislon OR aprednislone OR benisolon OR benisolone OR berisolon OR berisolone OR caberdelta OR capsoid OR "co hydeltra" OR codelcortone OR compresolon OR cortadeltona OR cortadeltone OR cortalone OR cortelinter OR cortisolone OR cotolone OR dacortin OR "dacortin h" OR dacrotin OR decaprednil OR "decortin h" OR decortril OR "dehydro cortex" OR "dehydro hydrocortisone" OR "dehydro hydrocortisone" OR dehydrocortex OR dehydrocortisol OR dehydrocortisole OR dehydrohydrocortison OR dehydrohydrocortisone OR delcortol OR "delta 1 17 hydroxycorticosterone 21 acetate OR delta 1 hydrocortisone" OR "delta cortef" OR "delta cortril" OR "delta ef cortelan" OR "delta f OR delta hycortol" OR "delta hydrocortisone" OR "delta hydrocortisone" OR "delta ophticor" OR "delta stab" OR "delta‐cortef" OR "delta1 dehydrocortisol" OR "delta1 dehydrohydrocortisone" OR "delta1 hydrocortisone" OR deltacortef OR deltacortenolo OR deltacortil OR deltacortoil OR deltacortril OR deltaderm OR deltaglycortril OR deltahycortol OR deltahydrocortison OR deltahydrocortisone OR deltaophticor OR deltasolone OR deltastab OR deltidrosol OR deltisilone OR deltisolon OR deltisolone OR deltolasson OR deltolassone OR deltosona OR deltosone OR dermosolon OR dhasolone OR DiAdresonF OR "di adreson f" OR "di adresone f" OR "diadreson f" OR "diadresone f" OR dicortol OR domucortone OR encortelon OR encortelone OR encortolon OR equisolon OR "fernisolone‐p" OR glistelone OR hefasolon OR "hostacortin h" OR hydeltra OR hydeltrone OR hydrelta OR hydrocortancyl OR hydrocortidelt OR hydrodeltalone OR hydrodeltisone OR hydroretrocortin OR hydroretrocortine OR inflanefran OR insolone OR "keteocort h" OR "key‐pred" OR lenisolone OR leocortol OR liquipred OR "lygal kopftinktur n" OR mediasolone OR meprisolon OR meprisolone OR metacortalon OR metacortalone OR metacortandralon OR metacortandralone OR metacortelone OR "meti derm" OR meticortelone OR metiderm OR morlone OR mydrapred OR "neo delta" OR nisolon OR nisolone OR "nsc 9120" OR nsc9120 OR opredsone OR panafcortelone OR panafcortolone OR panafort OR paracortol OR phlogex OR "pre cortisyl" OR preconin OR precortalon OR precortancyl OR precortisyl OR "pred‐ject‐50" OR "predacort 50" OR "predaject‐50" OR "predalone 50" OR predartrina OR predartrine OR predate OR predeltilone OR predisole OR predisyr OR "predne dome" OR prednecort OR prednedome OR prednelan OR "predni coelin" OR "predni h tablinen" OR "predni‐helvacort" OR prednicoelin OR prednicort OR prednicortelone OR "prednifor drops" OR predniment OR predniretard OR prednis OR prednisil OR prednisolon OR prednisolona OR prednivet OR prednorsolon OR prednorsolone OR predonine OR predorgasolona OR predorgasolone OR "pregna 1, 4 diene 11beta, 17alpha, 21 triol 3, 20 dione" OR prelon OR prelone OR prenilone OR prenin OR prenolone OR preventan OR prezolon OR rubycort OR scherisolon OR scherisolona OR serilone OR solondo OR solone OR solupren OR soluprene OR spiricort OR spolotane OR sterane OR sterolone OR supercortisol OR supercortizol OR taracortelone OR walesolone OR wysolone OR "50‐24‐8"
 #22 Methylprednisolone OR "adlone‐40" OR "adlone‐80" OR "dep medalone 80" OR depmedalone OR "depoject‐80" OR depopred OR esametone OR firmacort OR "med‐jec‐40" OR medixon OR mednin OR "medralone 80" OR medrate OR medrol OR medrone OR meprednisolone OR meprelon OR mesopren OR "methacort 40" OR "methacort 80" OR "methyl prednisolone" OR methylcotol OR methylcotolone OR "methylpred dp" OR methylsterolone OR metidrol OR metipred OR metrisone OR metycortin OR metypred OR metypresol OR neomedrone OR nsc 19987 OR nsc19987 OR prednol OR solomet OR "solu decortin" OR urbason OR "6923‐42‐8" OR "83‐43‐2"
 #23 Hydrocortisone OR acticort OR "aeroseb hc" OR "ala‐cort" OR "ala‐scalp" OR alfacort OR algicortis OR alkindi OR "alpha derm" OR alphaderm OR "anucort‐hc" OR "anumed‐hc" OR "anutone‐hc" OR "aquanil hc" OR "balneol‐hc" OR "barseb hc" OR "beta‐hc" OR biacort OR cetacort OR cobadex OR colocort OR "compound f" OR "cordicare lotion" OR coripen OR "cort dome" OR cortef OR cortenema OR cortibel OR corticorenol OR cortifair OR cortifan OR cortiphate OR cortisol OR cortisole OR cortispray OR cortoderm OR cortril OR cotacort OR covocort OR "cremicort‐h" OR cutaderm OR "derm‐aid cream" OR "dermacrin hc lotion" OR dermaid OR dermocare OR dermocortal OR dermolate OR dioderm OR eczacort OR "ef cortelan" OR efcortelan OR egocort OR eksalb OR eldecort OR "emo‐cort" OR epicort OR epicortisol OR ficortril OR filocot OR flexicort OR "gly‐cort" OR glycort OR "h‐cort" OR "hc no. 1" OR "hc no. 4" OR hebcort OR "hemorrhoidal hc" OR "hemril‐30" OR "hemril‐hc uniserts" OR "hi‐cor" OR hidrotisona OR hycor OR hycort OR hydracort OR hydrasson OR "hydro ricortex" OR "hydro‐rx" OR hydrocort OR hydrocorticosteroid OR hydrocortisate OR hydrocortison OR hydrocortisonum OR hydrocortisyl OR hydrocortone OR hydrogalen OR hydrokort OR hydrokortison OR hydrotopic OR hysone OR hytisone OR hytone OR "incortin h" OR "instacort 10" OR kyypakkaus OR "lacticare hc" OR "lemnis fatty cream hc" OR lenirit OR "medihaler cort" OR "medihaler duo" OR medrocil OR mildison OR "mitocortyl demangeaisons" OR munitren OR "nogenic hc" OR novohydrocort OR "nsc 10483" OR "nsc 741" OR nsc10483 OR nutracort OR optef OR "otosone f" OR penecort OR plenadren OR prepcort OR "prevex hc" OR "pro cort" OR procort OR "procto‐kit" OR proctocort OR "proctosert hc" OR "proctosol‐hc" OR proctosone OR "proctozone hc" OR procutan OR "rectasol‐hc" OR rectocort OR rederm OR sanatison OR "scalp‐aid" OR schericur OR "scherosone f" OR skincalm OR "stie‐cort" OR "substance m" OR synacort OR texacort OR "triburon‐hc" OR unicort OR vasocort OR "50‐23‐7"
 #24 Loteprednol OR alrex OR "cddd 5604" OR cddd5604 OR CEHOAC OR "chloromethyl 17alpha ethoxycarbonyloxy 11beta hydroxy 3 oxoandrosta 1, 4 diene 17 carboxylate" OR "hgp 1" OR hgp1 OR inveltys OR "kpi 121" OR kpi121 OR "le‐mpp" OR lotemax OR loterex OR loterox OR lotesoft OR "p 5604" OR p5604 OR "82034‐46‐6"
 #25 Rimexolone OR baxol OR "org 6216" OR org6216 OR "pregna 1, 4 dien 11beta ol 3, 20 dione, 16alpha, 17alpha, 21 trimethyl" OR rimexel OR trimexolone OR vexol OR vexolon OR "49697‐38‐3"
 #26 "Prednisolone acetate" OR "ak‐pred" OR deppredalone OR econopred OR "flo pred" OR "isopto cetapred" OR "key pred" OR "meticortelone acetate" OR "ocu‐pred" OR omnipred OR optilon OR "poly pred" OR "pred forte" OR "pred mild" OR predforte OR predmet OR "prednefrin sf" OR "predni h" OR "predni‐ophtal" OR prednigalen OR "prednisolone 17 acetate" OR "prednisolone 21 acetate" OR "prednisolone acetate suspension" OR savacort OR "Scherisolone‐Kristall suspension" OR ultracortensol OR ultracortinol OR "52‐21‐1" OR "52628‐64‐5"
 #27 Beclomethasone OR beclometasone OR "Asmabec Clickhaler" OR Ascocortonyl OR Beclamet OR "Beclo Asma" OR "Beclo AZU" OR Beclocort OR Beclomet OR "Bemedrex Easyhaler" OR Beclorhinol OR Sanasthmax OR Becloturmant OR Beclovent OR Beconase OR Becloforte OR Becodisk OR Becodisks OR Propaderm OR Becotide OR Sanasthmyl OR "Beconase AQ" OR Bronchocort OR Junik OR Qvar OR Ecobec OR Beclazone OR Ventolair OR Prolair OR Filair OR "AeroBec Forte" OR Aerobec OR "Nasobec Aqueous" OR Respocort OR Vancenase OR Vanceril OR Aldecin OR Viarin OR "4419‐39‐0"
 #28 Betamethasone OR adbeon OR becasone OR beprogel OR "beta methason" OR "beta methasone" OR "beta‐phos/ac" OR betacortril OR betadexamethasone OR betametasone OR betamethasolone OR betamethason OR betamethasonium OR betamethasonum OR betamethazone OR betason OR betnasol OR betnelan OR "betnesol h" OR "betnesol v" OR "betnovate a" OR betsolan OR betsolon OR betsopart OR celestan OR celestene OR celeston OR celestona OR celestone OR cellestoderm OR cidoten OR dermobet OR diprolen OR flubenisolone OR methasone OR "nsc 39470" OR nsc39470 OR "pregna 1, 4 diene 3, 20 dione 11, 17, 21 triol, 9 alpha fluoro 16beta methyl" OR "rg 833" OR rg833 OR rinderon OR "sch 4831" OR sch4831 OR walacort OR "378‐44‐9"
 #29 Budesonide OR acorspray OR aerox OR allercort OR aquacort OR "b cort" OR "bebe cream" OR bidien OR budecol OR budecort OR budefat OR budeflam OR budelin OR "budenase aq" OR budeno OR budenofalk OR budenoside OR budes OR budeson OR "budesonide easyhaler" OR budiair OR "budicort respules" OR "budo‐san" OR budon OR budosan OR bunase OR buparid OR butacort OR clebudan OR coramen OR cortiment OR cortimentmmx OR cycortide OR "desona nasal" OR desonix OR dexbudesonide OR duasma OR eltair OR entocir OR entocort OR esonide OR "giona easyhaler" OR horacort OR inflammide OR inflanaze OR intesticort OR intestifalk OR jorveza OR larbex OR "map 0010" OR map0010 OR miflo OR miflonid OR miflonide OR miflonil OR mikicort OR nebbud OR "neo‐rinactive" OR novopulmon OR numark OR olfex OR preferid OR "pregna 1, 4 diene 3, 20 dione 16, 17 butyraldehyde cyclic acetal, 11beta, 16alpha, 17, 21 tetrahydroxy" OR pulmaxan OR "pulmicon susp for nebulizer" OR "pulmicon susp for nebulizer" OR pulmicort OR pulmoliseflam OR pulmotide OR respicort OR rhinocort OR ribujet OR ribuspir OR ribuvent OR "s 1320" OR s1320 OR spirocort OR "tafen nasal" OR uceris OR "51333‐22‐3" OR "51372‐29‐3"
 #30 Ciclesonide OR alvesco OR "b 9207 015" OR "b 9207015" OR "b9207 015" OR "b9207015" OR "by 9010" OR "by9010" OR omnaris OR zetonna OR "126544‐47‐6"
 #31 Flunisolide OR aerobid OR aerospan OR bronalide OR bronilide OR cyntaris OR flunitec OR gibiflu OR inhacort OR locasyn OR lokilan OR "lunibron‐a" OR lunis OR nasalide OR nasarel OR rhinalar OR "rs 3999" OR rs3999 OR sanergal OR synaclyn OR syntaris OR "val 679" OR val679 OR "3385‐03‐3"
 #32 Fluticasone OR Flonase OR Flovent OR Cutivate OR Flixonase OR Flixotide OR "90566‐53‐3"
 #33 Mometasone OR "allermax aqueous" OR asmanex OR belloseta OR bloctimo OR breso OR brusonex OR cutticom OR dermotasone OR dermovel OR desdek OR ecural OR edelan OR elica OR elocom OR elocon OR elocyn OR elomet OR eloson OR flumeta OR frondava OR ivoxel OR kalmente OR lorome OR mefurosan OR metaspray OR metmin OR mipasu OR mofunder OR momate OR momeallerg OR momecutan OR momederm OR momegalen OR momekort OR momesonex OR momespir OR momester OR mometahexal OR mometason OR mometasone OR mometop OR mommox OR monovel OR monovo OR morecort OR motaderm OR mundoson OR muofuder OR nasehaler OR nasoaldo OR nasomet OR nasometin OR nasonex OR nasotasone OR netonox OR "novasone cream" OR "novasone lotion" OR "novasone ointment" OR ovison OR ovixan OR pronasal OR rinelon OR rinometasone OR rivelon OR "sch 32088" OR sch32088 OR sebanez OR sinuva OR sonalox OR temon OR uniclar OR zhekort OR "105102‐22‐5" OR "83919‐23‐7"
 #34 Triamcinolone OR acetocot OR adcortyl OR aristocort OR aristodan OR azmacor OR celeste OR "cl 19823" OR cl19823 OR clinacort OR clinalog OR delphicort OR fluoxiprednisolone OR fluoxyprednisolone OR "ken‐jec 40" OR kenacort OR korticoid OR ledercort OR omcilon OR polcortolon OR "rp 8357" OR rp8357 OR simacort OR sterocort OR "tac 3" OR tramcinolone OR triacortyl OR "triam‐a" OR "triam‐forte" OR triamcinolon OR triamcinolona OR triamcort OR triamcot OR "triamonide 40" OR triamsicort OR triancinolon OR "u‐tri‐lone" OR volon OR "124‐94‐7"
 #35 {OR #13‐#34}
 #36 #12 AND #35

Appendix 2. MEDLINE (Ovid) search strategy

1. Randomized Controlled Trial.pt.
 2. Controlled Clinical Trial.pt.
 3. (randomized or randomised).ab,ti.
 4. placebo.ab,ti.
 5. drug therapy.fs.
 6. randomly.ab,ti.
 7. trial.ab,ti.
 8. groups.ab,ti.
 9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8
 10. exp animals/ not humans.sh.
 11. 9 not 10
 12. exp Cellulitis/
 13. exp Orbital Cellulitis/
 14. ((periorbit* or orbit* or preseptal or "pre septal" or postseptal or "post septal") adj3 celluliti*).tw.
 15. ((subperiosteal or "sub periosteal" or orbital or intraconal) adj1 abscess*).tw.
 16. exp Eye Infections, Bacterial/
 17. (Bacterial adj3 eye infect*).tw.
 18. Orbital Diseases/
 19. (orbital adj1 disease*).tw.
 20. exp Sinusitis/
 21. (sinusitis or (sinus adj2 infect*) or rhinosinusitis).tw.
 22. "Sinus venous thrombosis".tw.
 23. or/12‐22
 24. exp Orbital Cellulitis/dt [Drug Therapy]
 25. exp Steroids/
 26. Steroid*.tw.
 27. exp Adrenal Cortex Hormones/
 28. (("Adrenal Cortex" adj1 Hormone*) or Corticosteroid* or Corticoid* or Glucocorticoid* or (Glucorticoid adj1 Effect*) or Hydroxycorticosteroid* or ("Adrenal cortical" adj1 hormone*) or (Adrenocortical adj1 hormone*) or Adrenocorticosteroid* or Dermocorticosteroid*).tw.
 29. (Glucocorticosteroid* or Glucocorticoidsteroid* or Glucocortoid* or Glycocorticoid* or Glycocorticosteroid*).tw.
 30. (Dexamethasone or adrecort or adrenocot or aeroseb dex or aflucoson or aflucosone or alfalyl or anaflogistico or arcodexan or arcodexane or artrosone or azium or bidexol or calonat or cebedex or cetadexon or colofoam or corsona or cortastat or cortidex or cortidexason or cortidrona or cortidrone or cortisumman or "dacortina fuerte" or "dacortine fuerte" or dalalone or danasone or "de‐sone la" or decacortin or decadeltosona or decadeltosone or decaderm or decadion or decadran or decadron or decadronal or decadrone or decaesadril or decaject or decameth or decamethasone or decasone or decaspray or decasterolone or decdan or decilone or decofluor or dectancyl or dekacort or delladec or deltafluoren or deltafluorene or dergramin or deronil or desacort or desacortone or desadrene or desalark or desameton or desametone or desigdron or "dexa cortisyl" or "dexa dabrosan" or "dexa korti" or "dexa scherosan" or "dexa scherozon" or "dexa scherozone" or "dexa‐p" or "dexacen 4" or dexachel or dexacort or dexacortal or dexacorten or dexacortin or dexacortisyl or dexadabroson or dexadecadrol or dexadrol or dexagel or dexagen or dexahelvacort or dexakorti or dexalien or dexalocal or dexame or dexamecortin or dexameson or dexamesone or dexametason or dexametasone or dexameth or dexamethason or dexamethazon or dexamethonium or dexamonozon or dexan or dexane or dexano or dexapot or dexascheroson or dexascherozon or dexascherozone or dexason or dexasone or dexinoral or dexionil or dexmethsone or dexona or dexone or dexpak or dextelan or dextrasone or dexycu or dezone or dibasona or doxamethasone or esacortene or "ex s1" or exadion or exadione or firmalone or "fluormethyl prednisolone" or fluormethylprednisolon or fluormethylprednisolone or fluormone or fluorocort or fluorodelta or fluoromethylprednisolone or fortecortin or gammacorten or gammacortene or grosodexon or grosodexone or hexadecadiol or hexadecadrol or hexadiol or hexadrol or isnacort or "isopto dex" or "isopto maxidex" or "isopto‐maxidex" or isoptodex or isoptomaxidex or "lokalison f" or loverine or luxazone or marvidione or maxidex or mediamethasone or megacortin or mephameson or mephamesone or metasolon or metasolone or "methazon ion" or "methazone ion" or methazonion or methazonione or methylfluorprednisolone or "metisone lafi" or mexasone or millicorten or millicortenol or "mk 125" or mk125 or mymethasone or neoforderx or neofordex or nisomethasona or novocort or "nsc 34521" or nsc34521 or "oftan‐dexa" or opticorten or opticortinol or oradexan or oradexon or oradexone or orgadrone or ozurdex or pidexon or policort or posurdex or "predni f tablinen" or "predni‐f" or "prednisolone f" or prodexona or prodexone or sanamethasone or santenson or santeson or sawasone or solurex or spoloven or sterasone or thilodexine or triamcimetil or vexamet or visumetazone or visumethazone or "50‐02‐2").tw.
 31. (Prednisone or ancortone or biocortone or colisone or cortan or cortancyl or cortidelt or cortiprex or cutason or dacorten or "de cortisyl" or decortancyl or dacortin or decortin or decortine or decortisyl or dehydrocortisone or dekortin or delitisone or "dellacort a" or "delta cortelan" or "delta cortisone" or "delta dome" or "delta e" or "delta prenovis" or deltacorten or deltacortene or deltacortisone or deltacortone or deltasone or deltison or deltisona or deltra or "di adreson" or diadreson or drazone or encorton or encortone or enkorton or enkortolon or fernisone or hostacortin or insone or "liquid pred" or lodotra or "me‐korti" or meprison or metacortandracin or meticorten or meticortine or nisona or "nsc 10023" or nsc10023 or orasone or orisane or panafcort or panasol or paracort or pehacort or precort or precortal or "predni tablinen" or "prednicen‐m" or prednicorm or prednicot or prednidib or predniment or prednison or prednitone or "pregna 1, 4 diene 3, 11, 20 trione 17, 21 diol" or pronison or pronisone or pronizone or pulmison or rayos or rectodelt or servisone or sone or steerometz or sterapred or ultracorten or urtilone or winpred or "53‐03‐2").tw.
 32. (Prednisolone or adelcort or antisolon or antisolone or aprednislon or aprednislone or benisolon or benisolone or berisolon or berisolone or caberdelta or capsoid or "co hydeltra" or codelcortone or compresolon or cortadeltona or cortadeltone or cortalone or cortelinter or cortisolone or cotolone or dacortin or "dacortin h" or dacrotin or decaprednil or "decortin h" or decortril or "dehydro cortex" or "dehydro hydrocortisone" or "dehydro hydrocortisone" or dehydrocortex or dehydrocortisol or dehydrocortisole or dehydrohydrocortison or dehydrohydrocortisone or delcortol or "delta 1 17 hydroxycorticosterone 21 acetate OR delta 1 hydrocortisone" or "delta cortef" or "delta cortril" or "delta ef cortelan" or "delta f OR delta hycortol" or "delta hydrocortisone" or "delta hydrocortisone" or "delta ophticor" or "delta stab" or "delta‐cortef" or "delta1 dehydrocortisol" or "delta1 dehydrohydrocortisone" or "delta1 hydrocortisone" or deltacortef or deltacortenolo or deltacortil or deltacortoil or deltacortril or deltaderm or deltaglycortril or deltahycortol or deltahydrocortison or deltahydrocortisone or deltaophticor or deltasolone or deltastab or deltidrosol or deltisilone or deltisolon or deltisolone or deltolasson or deltolassone or deltosona or deltosone or dermosolon or dhasolone or DiAdresonF or "di adreson f" or "di adresone f" or "diadreson f" or "diadresone f" or dicortol or domucortone or encortelon or encortelone or encortolon or equisolon or "fernisolone‐p" or glistelone or hefasolon or "hostacortin h" or hydeltra or hydeltrone or hydrelta or hydrocortancyl or hydrocortidelt or hydrodeltalone or hydrodeltisone or hydroretrocortin or hydroretrocortine or inflanefran or insolone or "keteocort h" or "key‐pred" or lenisolone or leocortol or liquipred or "lygal kopftinktur n" or mediasolone or meprisolon or meprisolone or metacortalon or metacortalone or metacortandralon or metacortandralone or metacortelone or "meti derm" or meticortelone or metiderm or morlone or mydrapred or "neo delta" or nisolon or nisolone or "nsc 9120" or nsc9120 or opredsone or panafcortelone or panafcortolone or panafort or paracortol or phlogex or "pre cortisyl" or preconin or precortalon or precortancyl or precortisyl or "pred‐ject‐50" or "predacort 50" or "predaject‐50" or "predalone 50" or predartrina or predartrine or predate or predeltilone or predisole or predisyr or "predne dome" or prednecort or prednedome or prednelan or "predni coelin" or "predni h tablinen" or "predni‐helvacort" or prednicoelin or prednicort or prednicortelone or "prednifor drops" or predniment or predniretard or prednis or prednisil or prednisolon or prednisolona or prednivet or prednorsolon or prednorsolone or predonine or predorgasolona or predorgasolone or "pregna 1, 4 diene 11beta, 17alpha, 21 triol 3, 20 dione" or prelon or prelone or prenilone or prenin or prenolone or preventan or prezolon or rubycort or scherisolon or scherisolona or serilone or solondo or solone or solupren or soluprene or spiricort or spolotane or sterane or sterolone or supercortisol or supercortizol or taracortelone or walesolone or wysolone or "50‐24‐8").tw.
 33. (Methylprednisolone or "adlone‐40" or "adlone‐80" or "dep medalone 80" or depmedalone or "depoject‐80" or depopred or esametone or firmacort or "med‐jec‐40" or medixon or mednin or "medralone 80" or medrate or medrol or medrone or meprednisolone or meprelon or mesopren or "methacort 40" or "methacort 80" or "methyl prednisolone" or methylcotol or methylcotolone or "methylpred dp" or methylsterolone or metidrol or metipred or metrisone or metycortin or metypred or metypresol or neomedrone or nsc 19987 or nsc19987 or prednol or solomet or "solu decortin" or urbason or "6923‐42‐8" or "83‐43‐2").tw.
 34. (Hydrocortisone or acticort or "aeroseb hc" or "ala‐cort" or "ala‐scalp" or alfacort or algicortis or alkindi or "alpha derm" or alphaderm or "anucort‐hc" or "anumed‐hc" or "anutone‐hc" or "aquanil hc" or "balneol‐hc" or "barseb hc" or "beta‐hc" or biacort or cetacort or cobadex or colocort or "compound f" or "cordicare lotion" or coripen or "cort dome" or cortef or cortenema or cortibel or corticorenol or cortifair or cortifan or cortiphate or cortisol or cortisole or cortispray or cortoderm or cortril or cotacort or covocort or "cremicort‐h" or cutaderm or "derm‐aid cream" or "dermacrin hc lotion" or dermaid or dermocare or dermocortal or dermolate or dioderm or eczacort or "ef cortelan" or efcortelan or egocort or eksalb or eldecort or "emo‐cort" or epicort or epicortisol or ficortril or filocot or flexicort or "gly‐cort" or glycort or "h‐cort" or "hc no. 1" or "hc no. 4" or hebcort or "hemorrhoidal hc" or "hemril‐30" or "hemril‐hc uniserts" or "hi‐cor" or hidrotisona or hycor or hycort or hydracort or hydrasson or "hydro ricortex" or "hydro‐rx" or hydrocort or hydrocorticosteroid or hydrocortisate or hydrocortison or hydrocortisonum or hydrocortisyl or hydrocortone or hydrogalen or hydrokort or hydrokortison or hydrotopic or hysone or hytisone or hytone or "incortin h" or "instacort 10" or kyypakkaus or "lacticare hc" or "lemnis fatty cream hc" or lenirit or "medihaler cort" or "medihaler duo" or medrocil or mildison or "mitocortyl demangeaisons" or munitren or "nogenic hc" or novohydrocort or "nsc 10483" or "nsc 741" or nsc10483 or nutracort or optef or "otosone f" or penecort or plenadren or prepcort or "prevex hc" or "pro cort" or procort or "procto‐kit" or proctocort or "proctosert hc" or "proctosol‐hc" or proctosone or "proctozone hc" or procutan or "rectasol‐hc" or rectocort or rederm or sanatison or "scalp‐aid" or schericur or "scherosone f" or skincalm or "stie‐cort" or "substance m" or synacort or texacort or "triburon‐hc" or unicort or vasocort or "50‐23‐7").tw.
 35. (Loteprednol or alrex or "cddd 5604" or cddd5604 or CEHOAC or "chloromethyl 17alpha ethoxycarbonyloxy 11beta hydroxy 3 oxoandrosta 1, 4 diene 17 carboxylate" or "hgp 1" or hgp1 or inveltys or "kpi 121" or kpi121 or "le‐mpp" or lotemax or loterex or loterox or lotesoft or "p 5604" or p5604 or "82034‐46‐6").tw.
 36. (Rimexolone or baxol or "org 6216" or org6216 or "pregna 1, 4 dien 11beta ol 3, 20 dione, 16alpha, 17alpha, 21 trimethyl" or rimexel or trimexolone or vexol or vexolon or "49697‐38‐3 #26 Prednisolone acetate" or "ak‐pred" or deppredalone or econopred or "flo pred" or "isopto cetapred" or "key pred" or "meticortelone acetate" or "ocu‐pred" or omnipred or optilon or "poly pred" or "pred forte" or "pred mild" or predforte or predmet or "prednefrin sf" or "predni h" or "predni‐ophtal" or prednigalen or "prednisolone 17 acetate" or "prednisolone 21 acetate" or "prednisolone acetate suspension" or savacort or "Scherisolone‐Kristall suspension" or ultracortensol or ultracortinol or "52‐21‐1" or "52628‐64‐5").tw.
 37. (Beclomethasone or beclometasone or "Asmabec Clickhaler" or Ascocortonyl or Beclamet or "Beclo Asma" or "Beclo AZU" or Beclocort or Beclomet or "Bemedrex Easyhaler" or Beclorhinol or Sanasthmax or Becloturmant or Beclovent or Beconase or Becloforte or Becodisk or Becodisks or Propaderm or Becotide or Sanasthmyl or "Beconase AQ" or Bronchocort or Junik or Qvar or Ecobec or Beclazone or Ventolair or Prolair or Filair or "AeroBec Forte" or Aerobec or "Nasobec Aqueous" or Respocort or Vancenase or Vanceril or Aldecin or Viarin or "4419‐39‐0").tw.
 38. (Betamethasone or adbeon or becasone or beprogel or "beta methason" or "beta methasone" or "beta‐phos/ac" or betacortril or betadexamethasone or betametasone or betamethasolone or betamethason or betamethasonium or betamethasonum or betamethazone or betason or betnasol or betnelan or "betnesol h" or "betnesol v" or "betnovate a" or betsolan or betsolon or betsopart or celestan or celestene or celeston or celestona or celestone or cellestoderm or cidoten or dermobet or diprolen or flubenisolone or methasone or "nsc 39470" or nsc39470 or "pregna 1, 4 diene 3, 20 dione 11, 17, 21 triol, 9 alpha fluoro 16beta methyl" or "rg 833" or rg833 or rinderon or "sch 4831" or sch4831 or walacort or "378‐44‐9").tw.
 39. (Budesonide or acorspray or aerox or allercort or aquacort or "b cort" or "bebe cream" or bidien or budecol or budecort or budefat or budeflam or budelin or "budenase aq" or budeno or budenofalk or budenoside or budes or budeson or "budesonide easyhaler" or budiair or "budicort respules" or "budo‐san" or budon or budosan or bunase or buparid or butacort or clebudan or coramen or cortiment or cortimentmmx or cycortide or "desona nasal" or desonix or dexbudesonide or duasma or eltair or entocir or entocort or esonide or "giona easyhaler" or horacort or inflammide or inflanaze or intesticort or intestifalk or jorveza or larbex or "map 0010" or map0010 or miflo or miflonid or miflonide or miflonil or mikicort or nebbud or "neo‐rinactive" or novopulmon or numark or olfex or preferid or "pregna 1, 4 diene 3, 20 dione 16, 17 butyraldehyde cyclic acetal, 11beta, 16alpha, 17, 21 tetrahydroxy" or pulmaxan or "pulmicon susp for nebulizer" or "pulmicon susp for nebulizer" or pulmicort or pulmoliseflam or pulmotide or respicort or rhinocort or ribujet or ribuspir or ribuvent or "s 1320" or s1320 or spirocort or "tafen nasal" or uceris or "51333‐22‐3" or "51372‐29‐3").tw.
 40. (Ciclesonide or alvesco or "b 9207 015" or "b 9207015" or "b9207 015" or "b9207015" or "by 9010" or "by9010" or omnaris or zetonna or "126544‐47‐6").tw.
 41. (Flunisolide or aerobid or aerospan or bronalide or bronilide or cyntaris or flunitec or gibiflu or inhacort or locasyn or lokilan or "lunibron‐a" or lunis or nasalide or nasarel or rhinalar or "rs 3999" or rs3999 or sanergal or synaclyn or syntaris or "val 679" or val679 or "3385‐03‐3").tw.
 42. (Fluticasone or Flonase or Flovent or Cutivate or Flixonase or Flixotide or "90566‐53‐3").tw.
 43. (Mometasone or "allermax aqueous" or asmanex or belloseta or bloctimo or breso or brusonex or cutticom or dermotasone or dermovel or desdek or ecural or edelan or elica or elocom or elocon or elocyn or elomet or eloson or flumeta or frondava or ivoxel or kalmente or lorome or mefurosan or metaspray or metmin or mipasu or mofunder or momate or momeallerg or momecutan or momederm or momegalen or momekort or momesonex or momespir or momester or mometahexal or mometason or mometasone or mometop or mommox or monovel or monovo or morecort or motaderm or mundoson or muofuder or nasehaler or nasoaldo or nasomet or nasometin or nasonex or nasotasone or netonox or "novasone cream" or "novasone lotion" or "novasone ointment" or ovison or ovixan or pronasal or rinelon or rinometasone or rivelon or "sch 32088" or sch32088 or sebanez or sinuva or sonalox or temon or uniclar or zhekort or "105102‐22‐5" or "83919‐23‐7").tw.
 44. (Triamcinolone or acetocot or adcortyl or aristocort or aristodan or azmacor or celeste or "cl 19823" or cl19823 or clinacort or clinalog or delphicort or fluoxiprednisolone or fluoxyprednisolone or "ken‐jec 40" or kenacort or korticoid or ledercort or omcilon or polcortolon or "rp 8357" or rp8357 or simacort or sterocort or "tac 3" or tramcinolone or triacortyl or "triam‐a" or "triam‐forte" or triamcinolon or triamcinolona or triamcort or triamcot or "triamonide 40" or triamsicort or triancinolon or "u‐tri‐lone" or volon or "124‐94‐7").tw.
 45. or/24‐44
 46. 23 and 45
 47. 11 and 46

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville et al (Glanville 2006).

Appendix 3. Embase.com search strategy

#1 'randomized controlled trial'/exp
 #2 'randomization'/exp
 #3 'double blind procedure'/exp
 #4 'single blind procedure'/exp
 #5 random*:ab,ti
 #6 #1 OR #2 OR #3 OR #4 OR #5
 #7 'animal'/exp OR 'animal experiment'/exp
 #8 'human'/exp
 #9 #7 AND #8
 #10 #7 NOT #9
 #11 #6 NOT #10
 #12 'clinical trial'/exp
 #13 (clin* NEAR/3 trial*):ab,ti
 #14 ((singl* OR doubl* OR trebl* OR tripl*) NEAR/3 (blind* OR mask*)):ab,ti
 #15 'placebo'/exp
 #16 placebo*:ab,ti
 #17 random*:ab,ti
 #18 'experimental design'/exp
 #19 'crossover procedure'/exp
 #20 'control group'/exp
 #21 'latin square design'/exp
 #22 #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21
 #23 #22 NOT #10
 #24 #23 NOT #11
 #25 'comparative study'/exp
 #26 'evaluation'/exp
 #27 'prospective study'/exp
 #28 control*:ab,ti OR prospectiv*:ab,ti OR volunteer*:ab,ti
 #29 #25 OR #26 OR #27 OR #28
 #30 #29 NOT #10
 #31 #30 NOT (#11 OR #23)
 #32 #11 OR #24 OR #31
 #33 'cellulitis'/exp
 #34 'orbit cellulitis'/exp
 #35 ((periorbit* OR orbit* OR preseptal OR 'pre septal' OR postseptal OR 'post septal') NEAR/3 celluliti*):ab,ti,kw
 #36 ((subperiosteal OR 'sub periosteal' OR orbital OR intraconal) NEXT/1 abscess*):ab,ti,kw
 #37 'bacterial eye infection'/exp
 #38 ((bacterial NEAR/3 'eye infect*':ab,ti,kw
 #39 'orbit disease'/de
 #40 (orbital NEXT/1 disease*):ab,ti,kw
 #41 'sinusitis'/exp
 #42 (sinusitis OR (sinus NEXT/2 infect*) OR rhinosinusitis):ab,ti,kw
 #43 'sinus venous thrombosis':ab,ti,kw
 #44 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40 OR #41 OR #42 OR #43
 #45 'orbit cellulitis'/exp AND 'drug therapy'/lnk
 #46 'steroid'/exp
 #47 steroid*:ab,ti,kw
 #48 'corticosteroid'/exp
 #49 ("Adrenal Cortex Hormone*" OR Corticosteroid* OR Corticoid* OR Glucocorticoid* OR "Glucorticoid Effect*" OR Hydroxycorticosteroid* OR "adrenal cortical hormone*" OR "adrenocortical hormone*" OR adrenocorticosteroid* OR dermocorticosteroid*):ab,ti,kw,tn
 #50 (glucocorticosteroid* OR glucocorticoidsteroid* OR glucocortoid* OR glycocorticoid* OR glycocorticosteroid*):ab,ti,kw,tn
 #51 (Dexamethasone OR adrecort OR adrenocot OR aeroseb dex OR aflucoson OR aflucosone OR alfalyl OR anaflogistico OR arcodexan OR arcodexane OR artrosone OR azium OR bidexol OR calonat OR cebedex OR cetadexon OR colofoam OR corsona OR cortastat OR cortidex OR cortidexason OR cortidrona OR cortidrone OR cortisumman OR "dacortina fuerte" OR "dacortine fuerte" OR dalalone OR danasone OR "de‐sone la" OR decacortin OR decadeltosona OR decadeltosone OR decaderm OR decadion OR decadran OR decadron OR decadronal OR decadrone OR decaesadril OR decaject OR decameth OR decamethasone OR decasone OR decaspray OR decasterolone OR decdan OR decilone OR decofluor OR dectancyl OR dekacort OR delladec OR deltafluoren OR deltafluorene OR dergramin OR deronil OR desacort OR desacortone OR desadrene OR desalark OR desameton OR desametone OR desigdron OR "dexa cortisyl" OR "dexa dabrosan" OR "dexa korti" OR "dexa scherosan" OR "dexa scherozon" OR "dexa scherozone" OR "dexa‐p" OR "dexacen 4" OR dexachel OR dexacort OR dexacortal OR dexacorten OR dexacortin OR dexacortisyl OR dexadabroson OR dexadecadrol OR dexadrol OR dexagel OR dexagen OR dexahelvacort OR dexakorti OR dexalien OR dexalocal OR dexame OR dexamecortin OR dexameson OR dexamesone OR dexametason OR dexametasone OR dexameth OR dexamethason OR dexamethazon OR dexamethonium OR dexamonozon OR dexan OR dexane OR dexano OR dexapot OR dexascheroson OR dexascherozon OR dexascherozone OR dexason OR dexasone OR dexinoral OR dexionil OR dexmethsone OR dexona OR dexone OR dexpak OR dextelan OR dextrasone OR dexycu OR dezone OR dibasona OR doxamethasone OR esacortene OR "ex s1" OR exadion OR exadione OR firmalone OR "fluormethyl prednisolone" OR fluormethylprednisolon OR fluormethylprednisolone OR fluormone OR fluorocort OR fluorodelta OR fluoromethylprednisolone OR fortecortin OR gammacorten OR gammacortene OR grosodexon OR grosodexone OR hexadecadiol OR hexadecadrol OR hexadiol OR hexadrol OR isnacort OR "isopto dex" OR "isopto maxidex" OR "isopto‐maxidex" OR isoptodex OR isoptomaxidex OR "lokalison f" OR loverine OR luxazone OR marvidione OR maxidex OR mediamethasone OR megacortin OR mephameson OR mephamesone OR metasolon OR metasolone OR "methazon ion" OR "methazone ion" OR methazonion OR methazonione OR methylfluorprednisolone OR "metisone lafi" OR mexasone OR millicorten OR millicortenol OR "mk 125" OR mk125 OR mymethasone OR neoforderx OR neofordex OR nisomethasona OR novocort OR "nsc 34521" OR nsc34521 OR "oftan‐dexa" OR opticorten OR opticortinol OR oradexan OR oradexon OR oradexone OR orgadrone OR ozurdex OR pidexon OR policort OR posurdex OR "predni f tablinen" OR "predni‐f" OR "prednisolone f" OR prodexona OR prodexone OR sanamethasone OR santenson OR santeson OR sawasone OR solurex OR spoloven OR sterasone OR thilodexine OR triamcimetil OR vexamet OR visumetazone OR visumethazone OR "50‐02‐2"):ab,ti,kw,tn
 #52 (Prednisone OR ancortone OR biocortone OR colisone OR cortan OR cortancyl OR cortidelt OR cortiprex OR cutason OR dacorten OR "de cortisyl" OR decortancyl OR dacortin OR decortin OR decortine OR decortisyl OR dehydrocortisone OR dekortin OR delitisone OR "dellacort a" OR "delta cortelan" OR "delta cortisone" OR "delta dome" OR "delta e" OR "delta prenovis" OR deltacorten OR deltacortene OR deltacortisone OR deltacortone OR deltasone OR deltison OR deltisona OR deltra OR "di adreson" OR diadreson OR drazone OR encorton OR encortone OR enkorton OR enkortolon OR fernisone OR hostacortin OR insone OR "liquid pred" OR lodotra OR "me‐korti" OR meprison OR metacortandracin OR meticorten OR meticortine OR nisona OR "nsc 10023" OR nsc10023 OR orasone OR orisane OR panafcort OR panasol OR paracort OR pehacort OR precort OR precortal OR "predni tablinen" OR "prednicen‐m" OR prednicorm OR prednicot OR prednidib OR predniment OR prednison OR prednitone OR "pregna 1, 4 diene 3, 11, 20 trione 17, 21 diol" OR pronison OR pronisone OR pronizone OR pulmison OR rayos OR rectodelt OR servisone OR sone OR steerometz OR sterapred OR ultracorten OR urtilone OR winpred OR "53‐03‐2"):ab,ti,kw,tn
 #53 (Prednisolone OR adelcort OR antisolon OR antisolone OR aprednislon OR aprednislone OR benisolon OR benisolone OR berisolon OR berisolone OR caberdelta OR capsoid OR "co hydeltra" OR codelcortone OR compresolon OR cortadeltona OR cortadeltone OR cortalone OR cortelinter OR cortisolone OR cotolone OR dacortin OR "dacortin h" OR dacrotin OR decaprednil OR "decortin h" OR decortril OR "dehydro cortex" OR "dehydro hydrocortisone" OR "dehydro hydrocortisone" OR dehydrocortex OR dehydrocortisol OR dehydrocortisole OR dehydrohydrocortison OR dehydrohydrocortisone OR delcortol OR "delta 1 17 hydroxycorticosterone 21 acetate OR delta 1 hydrocortisone" OR "delta cortef" OR "delta cortril" OR "delta ef cortelan" OR "delta f OR delta hycortol" OR "delta hydrocortisone" OR "delta hydrocortisone" OR "delta ophticor" OR "delta stab" OR "delta‐cortef" OR "delta1 dehydrocortisol" OR "delta1 dehydrohydrocortisone" OR "delta1 hydrocortisone" OR deltacortef OR deltacortenolo OR deltacortil OR deltacortoil OR deltacortril OR deltaderm OR deltaglycortril OR deltahycortol OR deltahydrocortison OR deltahydrocortisone OR deltaophticor OR deltasolone OR deltastab OR deltidrosol OR deltisilone OR deltisolon OR deltisolone OR deltolasson OR deltolassone OR deltosona OR deltosone OR dermosolon OR dhasolone OR DiAdresonF OR "di adreson f" OR "di adresone f" OR "diadreson f" OR "diadresone f" OR dicortol OR domucortone OR encortelon OR encortelone OR encortolon OR equisolon OR "fernisolone‐p" OR glistelone OR hefasolon OR "hostacortin h" OR hydeltra OR hydeltrone OR hydrelta OR hydrocortancyl OR hydrocortidelt OR hydrodeltalone OR hydrodeltisone OR hydroretrocortin OR hydroretrocortine OR inflanefran OR insolone OR "keteocort h" OR "key‐pred" OR lenisolone OR leocortol OR liquipred OR "lygal kopftinktur n" OR mediasolone OR meprisolon OR meprisolone OR metacortalon OR metacortalone OR metacortandralon OR metacortandralone OR metacortelone OR "meti derm" OR meticortelone OR metiderm OR morlone OR mydrapred OR "neo delta" OR nisolon OR nisolone OR "nsc 9120" OR nsc9120 OR opredsone OR panafcortelone OR panafcortolone OR panafort OR paracortol OR phlogex OR "pre cortisyl" OR preconin OR precortalon OR precortancyl OR precortisyl OR "pred‐ject‐50" OR "predacort 50" OR "predaject‐50" OR "predalone 50" OR predartrina OR predartrine OR predate OR predeltilone OR predisole OR predisyr OR "predne dome" OR prednecort OR prednedome OR prednelan OR "predni coelin" OR "predni h tablinen" OR "predni‐helvacort" OR prednicoelin OR prednicort OR prednicortelone OR "prednifor drops" OR predniment OR predniretard OR prednis OR prednisil OR prednisolon OR prednisolona OR prednivet OR prednorsolon OR prednorsolone OR predonine OR predorgasolona OR predorgasolone OR "pregna 1, 4 diene 11beta, 17alpha, 21 triol 3, 20 dione" OR prelon OR prelone OR prenilone OR prenin OR prenolone OR preventan OR prezolon OR rubycort OR scherisolon OR scherisolona OR serilone OR solondo OR solone OR solupren OR soluprene OR spiricort OR spolotane OR sterane OR sterolone OR supercortisol OR supercortizol OR taracortelone OR walesolone OR wysolone OR "50‐24‐8"):ab,ti,kw,tn
 #54 (Methylprednisolone OR "adlone‐40" OR "adlone‐80" OR "dep medalone 80" OR depmedalone OR "depoject‐80" OR depopred OR esametone OR firmacort OR "med‐jec‐40" OR medixon OR mednin OR "medralone 80" OR medrate OR medrol OR medrone OR meprednisolone OR meprelon OR mesopren OR "methacort 40" OR "methacort 80" OR "methyl prednisolone" OR methylcotol OR methylcotolone OR "methylpred dp" OR methylsterolone OR metidrol OR metipred OR metrisone OR metycortin OR metypred OR metypresol OR neomedrone OR nsc 19987 OR nsc19987 OR prednol OR solomet OR "solu decortin" OR urbason OR "6923‐42‐8" OR "83‐43‐2"):ab,ti,kw,tn
 #55 (Hydrocortisone OR acticort OR "aeroseb hc" OR "ala‐cort" OR "ala‐scalp" OR alfacort OR algicortis OR alkindi OR "alpha derm" OR alphaderm OR "anucort‐hc" OR "anumed‐hc" OR "anutone‐hc" OR "aquanil hc" OR "balneol‐hc" OR "barseb hc" OR "beta‐hc" OR biacort OR cetacort OR cobadex OR colocort OR "compound f" OR "cordicare lotion" OR coripen OR "cort dome" OR cortef OR cortenema OR cortibel OR corticorenol OR cortifair OR cortifan OR cortiphate OR cortisol OR cortisole OR cortispray OR cortoderm OR cortril OR cotacort OR covocort OR "cremicort‐h" OR cutaderm OR "derm‐aid cream" OR "dermacrin hc lotion" OR dermaid OR dermocare OR dermocortal OR dermolate OR dioderm OR eczacort OR "ef cortelan" OR efcortelan OR egocort OR eksalb OR eldecort OR "emo‐cort" OR epicort OR epicortisol OR ficortril OR filocot OR flexicort OR "gly‐cort" OR glycort OR "h‐cort" OR "hc no. 1" OR "hc no. 4" OR hebcort OR "hemorrhoidal hc" OR "hemril‐30" OR "hemril‐hc uniserts" OR "hi‐cor" OR hidrotisona OR hycor OR hycort OR hydracort OR hydrasson OR "hydro ricortex" OR "hydro‐rx" OR hydrocort OR hydrocorticosteroid OR hydrocortisate OR hydrocortison OR hydrocortisonum OR hydrocortisyl OR hydrocortone OR hydrogalen OR hydrokort OR hydrokortison OR hydrotopic OR hysone OR hytisone OR hytone OR "incortin h" OR "instacort 10" OR kyypakkaus OR "lacticare hc" OR "lemnis fatty cream hc" OR lenirit OR "medihaler cort" OR "medihaler duo" OR medrocil OR mildison OR "mitocortyl demangeaisons" OR munitren OR "nogenic hc" OR novohydrocort OR "nsc 10483" OR "nsc 741" OR nsc10483 OR nutracort OR optef OR "otosone f" OR penecort OR plenadren OR prepcort OR "prevex hc" OR "pro cort" OR procort OR "procto‐kit" OR proctocort OR "proctosert hc" OR "proctosol‐hc" OR proctosone OR "proctozone hc" OR procutan OR "rectasol‐hc" OR rectocort OR rederm OR sanatison OR "scalp‐aid" OR schericur OR "scherosone f" OR skincalm OR "stie‐cort" OR "substance m" OR synacort OR texacort OR "triburon‐hc" OR unicort OR vasocort OR "50‐23‐7"):ab,ti,kw,tn
 #56 (Loteprednol OR alrex OR "cddd 5604" OR cddd5604 OR CEHOAC OR "chloromethyl 17alpha ethoxycarbonyloxy 11beta hydroxy 3 oxoandrosta 1, 4 diene 17 carboxylate" OR "hgp 1" OR hgp1 OR inveltys OR "kpi 121" OR kpi121 OR "le‐mpp" OR lotemax OR loterex OR loterox OR lotesoft OR "p 5604" OR p5604 OR "82034‐46‐6"):ab,ti,kw,tn
 #57 (Rimexolone OR baxol OR "org 6216" OR org6216 OR "pregna 1, 4 dien 11beta ol 3, 20 dione, 16alpha, 17alpha, 21 trimethyl" OR rimexel OR trimexolone OR vexol OR vexolon OR "49697‐38‐3"):ab,ti,kw,tn
 #58 ("Prednisolone acetate" OR "ak‐pred" OR deppredalone OR econopred OR "flo pred" OR "isopto cetapred" OR "key pred" OR "meticortelone acetate" OR "ocu‐pred" OR omnipred OR optilon OR "poly pred" OR "pred forte" OR "pred mild" OR predforte OR predmet OR "prednefrin sf" OR "predni h" OR "predni‐ophtal" OR prednigalen OR "prednisolone 17 acetate" OR "prednisolone 21 acetate" OR "prednisolone acetate suspension" OR savacort OR "Scherisolone‐Kristall suspension" OR ultracortensol OR ultracortinol OR "52‐21‐1" OR "52628‐64‐5"):ab,ti,kw,tn
 #59 (Beclomethasone OR beclometasone OR "Asmabec Clickhaler" OR Ascocortonyl OR Beclamet OR "Beclo Asma" OR "Beclo AZU" OR Beclocort OR Beclomet OR "Bemedrex Easyhaler" OR Beclorhinol OR Sanasthmax OR Becloturmant OR Beclovent OR Beconase OR Becloforte OR Becodisk OR Becodisks OR Propaderm OR Becotide OR Sanasthmyl OR "Beconase AQ" OR Bronchocort OR Junik OR Qvar OR Ecobec OR Beclazone OR Ventolair OR Prolair OR Filair OR "AeroBec Forte" OR Aerobec OR "Nasobec Aqueous" OR Respocort OR Vancenase OR Vanceril OR Aldecin OR Viarin OR "4419‐39‐0"):ab,ti,kw,tn
 #60 (Betamethasone OR adbeon OR becasone OR beprogel OR "beta methason" OR "beta methasone" OR "beta‐phos/ac" OR betacortril OR betadexamethasone OR betametasone OR betamethasolone OR betamethason OR betamethasonium OR betamethasonum OR betamethazone OR betason OR betnasol OR betnelan OR "betnesol h" OR "betnesol v" OR "betnovate a" OR betsolan OR betsolon OR betsopart OR celestan OR celestene OR celeston OR celestona OR celestone OR cellestoderm OR cidoten OR dermobet OR diprolen OR flubenisolone OR methasone OR "nsc 39470" OR nsc39470 OR "pregna 1, 4 diene 3, 20 dione 11, 17, 21 triol, 9 alpha fluoro 16beta methyl" OR "rg 833" OR rg833 OR rinderon OR "sch 4831" OR sch4831 OR walacort OR "378‐44‐9"):ab,ti,kw,tn
 #61 (Budesonide OR acorspray OR aerox OR allercort OR aquacort OR "b cort" OR "bebe cream" OR bidien OR budecol OR budecort OR budefat OR budeflam OR budelin OR "budenase aq" OR budeno OR budenofalk OR budenoside OR budes OR budeson OR "budesonide easyhaler" OR budiair OR "budicort respules" OR "budo‐san" OR budon OR budosan OR bunase OR buparid OR butacort OR clebudan OR coramen OR cortiment OR cortimentmmx OR cycortide OR "desona nasal" OR desonix OR dexbudesonide OR duasma OR eltair OR entocir OR entocort OR esonide OR "giona easyhaler" OR horacort OR inflammide OR inflanaze OR intesticort OR intestifalk OR jorveza OR larbex OR "map 0010" OR map0010 OR miflo OR miflonid OR miflonide OR miflonil OR mikicort OR nebbud OR "neo‐rinactive" OR novopulmon OR numark OR olfex OR preferid OR "pregna 1, 4 diene 3, 20 dione 16, 17 butyraldehyde cyclic acetal, 11beta, 16alpha, 17, 21 tetrahydroxy" OR pulmaxan OR "pulmicon susp for nebulizer" OR "pulmicon susp for nebulizer" OR pulmicort OR pulmoliseflam OR pulmotide OR respicort OR rhinocort OR ribujet OR ribuspir OR ribuvent OR "s 1320" OR s1320 OR spirocort OR "tafen nasal" OR uceris OR "51333‐22‐3" OR "51372‐29‐3"):ab,ti,kw,tn
 #62 (Ciclesonide OR alvesco OR "b 9207 015" OR "b 9207015" OR "b9207 015" OR "b9207015" OR "by 9010" OR "by9010" OR omnaris OR zetonna OR "126544‐47‐6"):ab,ti,kw,tn
 #63 (Flunisolide OR aerobid OR aerospan OR bronalide OR bronilide OR cyntaris OR flunitec OR gibiflu OR inhacort OR locasyn OR lokilan OR "lunibron‐a" OR lunis OR nasalide OR nasarel OR rhinalar OR "rs 3999" OR rs3999 OR sanergal OR synaclyn OR syntaris OR "val 679" OR val679 OR "3385‐03‐3"):ab,ti,kw,tn
 #64 (Fluticasone OR Flonase OR Flovent OR Cutivate OR Flixonase OR Flixotide OR "90566‐53‐3"):ab,ti,kw,tn
 #65 (Mometasone OR "allermax aqueous" OR asmanex OR belloseta OR bloctimo OR breso OR brusonex OR cutticom OR dermotasone OR dermovel OR desdek OR ecural OR edelan OR elica OR elocom OR elocon OR elocyn OR elomet OR eloson OR flumeta OR frondava OR ivoxel OR kalmente OR lorome OR mefurosan OR metaspray OR metmin OR mipasu OR mofunder OR momate OR momeallerg OR momecutan OR momederm OR momegalen OR momekort OR momesonex OR momespir OR momester OR mometahexal OR mometason OR mometasone OR mometop OR mommox OR monovel OR monovo OR morecort OR motaderm OR mundoson OR muofuder OR nasehaler OR nasoaldo OR nasomet OR nasometin OR nasonex OR nasotasone OR netonox OR "novasone cream" OR "novasone lotion" OR "novasone ointment" OR ovison OR ovixan OR pronasal OR rinelon OR rinometasone OR rivelon OR "sch 32088" OR sch32088 OR sebanez OR sinuva OR sonalox OR temon OR uniclar OR zhekort OR "105102‐22‐5" OR "83919‐23‐7"):ab,ti,kw,tn
 #66 (Triamcinolone OR acetocot OR adcortyl OR aristocort OR aristodan OR azmacor OR celeste OR "cl 19823" OR cl19823 OR clinacort OR clinalog OR delphicort OR fluoxiprednisolone OR fluoxyprednisolone OR "ken‐jec 40" OR kenacort OR korticoid OR ledercort OR omcilon OR polcortolon OR "rp 8357" OR rp8357 OR simacort OR sterocort OR "tac 3" OR tramcinolone OR triacortyl OR "triam‐a" OR "triam‐forte" OR triamcinolon OR triamcinolona OR triamcort OR triamcot OR "triamonide 40" OR triamsicort OR triancinolon OR "u‐tri‐lone" OR volon OR "124‐94‐7"):ab,ti,kw,tn
 #67 #45 OR #46 OR #47 OR #48 OR #49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56 OR #57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64 OR #65 OR #66
 #68 #44 AND #67
 #69 #32 AND #68

Appendix 4. PubMed search strategy

1. ((randomized controlled trial[pt]) OR (controlled clinical trial[pt]) OR (randomised[tiab] OR randomized[tiab]) OR (placebo[tiab]) OR (drug therapy[sh]) OR (randomly[tiab]) OR (trial[tiab]) OR (groups[tiab])) NOT (animals[mh] NOT humans[mh])
 2. ((periorbit*[tw] OR orbit*[tw] OR preseptal[tw] OR "pre septal"[tw] OR postseptal[tw] OR "post septal"[tw]) AND celluliti*[tw])
 3. ((subperiosteal[tw] OR "sub periosteal"[tw] OR orbital[tw] OR intraconal[tw]) AND abscess*[tw])
 4. bacterial eye infect*[tw]
 5. orbital disease*[tw]
 6. sinusitis[tw] OR sinus infect*[tw] OR rhinosinusitis[tw]
 7. sinus venous thrombosis[tw]
 8. #2 OR #3 OR #4 OR #5 OR #6 OR #7
 9. steroid*[tw]
 10. Adrenal Cortex Hormone*[tw] OR Corticosteroid*[tw] OR Corticoid*[tw] OR Glucocorticoid*[tw] OR Glucorticoid Effect*[tw] OR Hydroxycorticosteroid*[tw] OR Adrenal cortical hormone*[tw] OR Adrenocortical hormone*[tw] OR Adrenocorticosteroid*[tw] OR Dermocorticosteroid*[tw]
 11. Glucocorticosteroid*[tw] OR Glucocorticoidsteroid*[tw] OR Glucocortoid*[tw] OR Glycocorticoid*[tw] OR Glycocorticosteroid*[tw]
 12. Dexamethasone[tw] OR adrecort[tw] OR adrenocot[tw] OR "aeroseb dex"[tw] OR aflucoson[tw] OR aflucosone[tw] OR alfalyl[tw] OR anaflogistico[tw] OR arcodexan[tw] OR arcodexane[tw] OR artrosone[tw] OR azium[tw] OR bidexol[tw] OR calonat[tw] OR cebedex[tw] OR cetadexon[tw] OR colofoam[tw] OR corsona[tw] OR cortastat[tw] OR cortidex[tw] OR cortidexason[tw] OR cortidrona[tw] OR cortidrone[tw] OR cortisumman[tw] OR "dacortina fuerte"[tw] OR "dacortine fuerte"[tw] OR dalalone[tw] OR danasone[tw] OR "de‐sone la"[tw] OR decacortin[tw] OR decadeltosona[tw] OR decadeltosone[tw] OR decaderm[tw] OR decadion[tw] OR decadran[tw] OR decadron[tw] OR decadronal[tw] OR decadrone[tw] OR decaesadril[tw] OR decaject[tw] OR decameth[tw] OR decamethasone[tw] OR decasone[tw] OR decaspray[tw] OR decasterolone[tw] OR decdan[tw] OR decilone[tw] OR decofluor[tw] OR dectancyl[tw] OR dekacort[tw] OR delladec[tw] OR deltafluoren[tw] OR deltafluorene[tw] OR dergramin[tw] OR deronil[tw] OR desacort[tw] OR desacortone[tw] OR desadrene[tw] OR desalark[tw] OR desameton[tw] OR desametone[tw] OR desigdron[tw] OR "dexa cortisyl"[tw] OR "dexa dabrosan"[tw] OR "dexa korti"[tw] OR "dexa scherosan"[tw] OR "dexa scherozon"[tw] OR "dexa scherozone"[tw] OR "dexa‐p"[tw] OR "dexacen 4"[tw] OR dexachel[tw] OR dexacort[tw] OR dexacortal[tw] OR dexacorten[tw] OR dexacortin[tw] OR dexacortisyl[tw] OR dexadabroson[tw] OR dexadecadrol[tw] OR dexadrol[tw] OR dexagel[tw] OR dexagen[tw] OR dexahelvacort[tw] OR dexakorti[tw] OR dexalien[tw] OR dexalocal[tw] OR dexame[tw] OR dexamecortin[tw] OR dexameson[tw] OR dexamesone[tw] OR dexametason[tw] OR dexametasone[tw] OR dexameth[tw] OR dexamethason[tw] OR dexamethazon[tw] OR dexamethonium[tw] OR dexamonozon[tw] OR dexan[tw] OR dexane[tw] OR dexano[tw] OR dexapot[tw] OR dexascheroson[tw] OR dexascherozon[tw] OR dexascherozone[tw] OR dexason[tw] OR dexasone[tw] OR dexinoral[tw] OR dexionil[tw] OR dexmethsone[tw] OR dexona[tw] OR dexone[tw] OR dexpak[tw] OR dextelan[tw] OR dextrasone[tw] OR dexycu[tw] OR dezone[tw] OR dibasona[tw] OR doxamethasone[tw] OR esacortene[tw] OR "ex s1"[tw] OR exadion[tw] OR exadione[tw] OR firmalone[tw] OR "fluormethyl prednisolone"[tw] OR fluormethylprednisolon[tw] OR fluormethylprednisolone[tw] OR fluormone[tw] OR fluorocort[tw] OR fluorodelta[tw] OR fluoromethylprednisolone[tw] OR fortecortin[tw] OR gammacorten[tw] OR gammacortene[tw] OR grosodexon[tw] OR grosodexone[tw] OR hexadecadiol[tw] OR hexadecadrol[tw] OR hexadiol[tw] OR hexadrol[tw] OR isnacort[tw] OR "isopto dex"[tw] OR "isopto maxidex"[tw] OR "isopto‐maxidex"[tw] OR isoptodex[tw] OR isoptomaxidex[tw] OR "lokalison f"[tw] OR loverine[tw] OR luxazone[tw] OR marvidione[tw] OR maxidex[tw] OR mediamethasone[tw] OR megacortin[tw] OR mephameson[tw] OR mephamesone[tw] OR metasolon[tw] OR metasolone[tw] OR "methazon ion"[tw] OR "methazone ion"[tw] OR methazonion[tw] OR methazonione[tw] OR methylfluorprednisolone[tw] OR "metisone lafi"[tw] OR mexasone[tw] OR millicorten[tw] OR millicortenol[tw] OR "mk 125"[tw] OR mk125[tw] OR mymethasone[tw] OR neoforderx[tw] OR neofordex[tw] OR nisomethasona[tw] OR novocort[tw] OR "nsc 34521"[tw] OR nsc34521[tw] OR "oftan‐dexa"[tw] OR opticorten[tw] OR opticortinol[tw] OR oradexan[tw] OR oradexon[tw] OR oradexone[tw] OR orgadrone[tw] OR ozurdex[tw] OR pidexon[tw] OR policort[tw] OR posurdex[tw] OR "predni f tablinen"[tw] OR "predni‐f"[tw] OR "prednisolone f"[tw] OR prodexona[tw] OR prodexone[tw] OR sanamethasone[tw] OR santenson[tw] OR santeson[tw] OR sawasone[tw] OR solurex[tw] OR spoloven[tw] OR sterasone[tw] OR thilodexine[tw] OR triamcimetil[tw] OR vexamet[tw] OR visumetazone[tw] OR visumethazone[tw] OR "50‐02‐2"[tw]
 13. Prednisone[tw] OR ancortone[tw] OR biocortone[tw] OR colisone[tw] OR cortan[tw] OR cortancyl[tw] OR cortidelt[tw] OR cortiprex[tw] OR cutason[tw] OR dacorten[tw] OR "de cortisyl"[tw] OR decortancyl[tw] OR dacortin[tw] OR decortin[tw] OR decortine[tw] OR decortisyl[tw] OR dehydrocortisone[tw] OR dekortin[tw] OR delitisone[tw] OR "dellacort a"[tw] OR "delta cortelan"[tw] OR "delta cortisone"[tw] OR "delta dome"[tw] OR "delta e"[tw] OR "delta prenovis"[tw] OR deltacorten[tw] OR deltacortene[tw] OR deltacortisone[tw] OR deltacortone[tw] OR deltasone[tw] OR deltison[tw] OR deltisona[tw] OR deltra[tw] OR "di adreson"[tw] OR diadreson[tw] OR drazone[tw] OR encorton[tw] OR encortone[tw] OR enkorton[tw] OR enkortolon[tw] OR fernisone[tw] OR hostacortin[tw] OR insone[tw] OR "liquid pred"[tw] OR lodotra[tw] OR "me‐korti"[tw] OR meprison[tw] OR metacortandracin[tw] OR meticorten[tw] OR meticortine[tw] OR nisona[tw] OR "nsc 10023"[tw] OR nsc10023[tw] OR orasone[tw] OR orisane[tw] OR panafcort[tw] OR panasol[tw] OR paracort[tw] OR pehacort[tw] OR precort[tw] OR precortal[tw] OR "predni tablinen"[tw] OR "prednicen‐m"[tw] OR prednicorm[tw] OR prednicot[tw] OR prednidib[tw] OR predniment[tw] OR prednison[tw] OR prednitone[tw] OR "pregna 1, 4 diene 3, 11, 20 trione 17, 21 diol"[tw] OR pronison[tw] OR pronisone[tw] OR pronizone[tw] OR pulmison[tw] OR rayos[tw] OR rectodelt[tw] OR servisone[tw] OR sone[tw] OR steerometz[tw] OR sterapred[tw] OR ultracorten[tw] OR urtilone[tw] OR winpred[tw] OR "53‐03‐2"[tw]
 14. Prednisolone[tw] OR adelcort[tw] OR antisolon[tw] OR antisolone[tw] OR aprednislon[tw] OR aprednislone[tw] OR benisolon[tw] OR benisolone[tw] OR berisolon[tw] OR berisolone[tw] OR caberdelta[tw] OR capsoid[tw] OR "co hydeltra"[tw] OR codelcortone[tw] OR compresolon[tw] OR cortadeltona[tw] OR cortadeltone[tw] OR cortalone[tw] OR cortelinter[tw] OR cortisolone[tw] OR cotolone[tw] OR dacortin[tw] OR "dacortin h"[tw] OR dacrotin[tw] OR decaprednil[tw] OR "decortin h"[tw] OR decortril[tw] OR "dehydro cortex"[tw] OR "dehydro hydrocortisone"[tw] OR "dehydro hydrocortisone"[tw] OR dehydrocortex[tw] OR dehydrocortisol[tw] OR dehydrocortisole[tw] OR dehydrohydrocortison[tw] OR dehydrohydrocortisone[tw] OR delcortol[tw] OR "delta 1 17 hydroxycorticosterone 21 acetate[tw] OR delta 1 hydrocortisone"[tw] OR "delta cortef"[tw] OR "delta cortril"[tw] OR "delta ef cortelan"[tw] OR "delta f[tw] OR delta hycortol"[tw] OR "delta hydrocortisone"[tw] OR "delta hydrocortisone"[tw] OR "delta ophticor"[tw] OR "delta stab"[tw] OR "delta‐cortef"[tw] OR "delta1 dehydrocortisol"[tw] OR "delta1 dehydrohydrocortisone"[tw] OR "delta1 hydrocortisone"[tw] OR deltacortef[tw] OR deltacortenolo[tw] OR deltacortil[tw] OR deltacortoil[tw] OR deltacortril[tw] OR deltaderm[tw] OR deltaglycortril[tw] OR deltahycortol[tw] OR deltahydrocortison[tw] OR deltahydrocortisone[tw] OR deltaophticor[tw] OR deltasolone[tw] OR deltastab[tw] OR deltidrosol[tw] OR deltisilone[tw] OR deltisolon[tw] OR deltisolone[tw] OR deltolasson[tw] OR deltolassone[tw] OR deltosona[tw] OR deltosone[tw] OR dermosolon[tw] OR dhasolone[tw] OR DiAdresonF[tw] OR "di adreson f"[tw] OR "di adresone f"[tw] OR "diadreson f"[tw] OR "diadresone f"[tw] OR dicortol[tw] OR domucortone[tw] OR encortelon[tw] OR encortelone[tw] OR encortolon[tw] OR equisolon[tw] OR "fernisolone‐p"[tw] OR glistelone[tw] OR hefasolon[tw] OR "hostacortin h"[tw] OR hydeltra[tw] OR hydeltrone[tw] OR hydrelta[tw] OR hydrocortancyl[tw] OR hydrocortidelt[tw] OR hydrodeltalone[tw] OR hydrodeltisone[tw] OR hydroretrocortin[tw] OR hydroretrocortine[tw] OR inflanefran[tw] OR insolone[tw] OR "keteocort h"[tw] OR "key‐pred"[tw] OR lenisolone[tw] OR leocortol[tw] OR liquipred[tw] OR "lygal kopftinktur n"[tw] OR mediasolone[tw] OR meprisolon[tw] OR meprisolone[tw] OR metacortalon[tw] OR metacortalone[tw] OR metacortandralon[tw] OR metacortandralone[tw] OR metacortelone[tw] OR "meti derm"[tw] OR meticortelone[tw] OR metiderm[tw] OR morlone[tw] OR mydrapred[tw] OR "neo delta"[tw] OR nisolon[tw] OR nisolone[tw] OR "nsc 9120"[tw] OR nsc9120[tw] OR opredsone[tw] OR panafcortelone[tw] OR panafcortolone[tw] OR panafort[tw] OR paracortol[tw] OR phlogex[tw] OR "pre cortisyl"[tw] OR preconin[tw] OR precortalon[tw] OR precortancyl[tw] OR precortisyl[tw] OR "pred‐ject‐50"[tw] OR "predacort 50"[tw] OR "predaject‐50"[tw] OR "predalone 50"[tw] OR predartrina[tw] OR predartrine[tw] OR predate[tw] OR predeltilone[tw] OR predisole[tw] OR predisyr[tw] OR "predne dome"[tw] OR prednecort[tw] OR prednedome[tw] OR prednelan[tw] OR "predni coelin"[tw] OR "predni h tablinen"[tw] OR "predni‐helvacort"[tw] OR prednicoelin[tw] OR prednicort[tw] OR prednicortelone[tw] OR "prednifor drops"[tw] OR predniment[tw] OR predniretard[tw] OR prednis[tw] OR prednisil[tw] OR prednisolon[tw] OR prednisolona[tw] OR prednivet[tw] OR prednorsolon[tw] OR prednorsolone[tw] OR predonine[tw] OR predorgasolona[tw] OR predorgasolone[tw] OR "pregna 1, 4 diene 11beta, 17alpha, 21 triol 3, 20 dione"[tw] OR prelon[tw] OR prelone[tw] OR prenilone[tw] OR prenin[tw] OR prenolone[tw] OR preventan[tw] OR prezolon[tw] OR rubycort[tw] OR scherisolon[tw] OR scherisolona[tw] OR serilone[tw] OR solondo[tw] OR solone[tw] OR solupren[tw] OR soluprene[tw] OR spiricort[tw] OR spolotane[tw] OR sterane[tw] OR sterolone[tw] OR supercortisol[tw] OR supercortizol[tw] OR taracortelone[tw] OR walesolone[tw] OR wysolone[tw] OR "50‐24‐8"[tw]
 15. Methylprednisolone[tw] OR "adlone‐40"[tw] OR "adlone‐80"[tw] OR "dep medalone 80"[tw] OR depmedalone[tw] OR "depoject‐80"[tw] OR depopred[tw] OR esametone[tw] OR firmacort[tw] OR "med‐jec‐40"[tw] OR medixon[tw] OR mednin[tw] OR "medralone 80"[tw] OR medrate[tw] OR medrol[tw] OR medrone[tw] OR meprednisolone[tw] OR meprelon[tw] OR mesopren[tw] OR "methacort 40"[tw] OR "methacort 80"[tw] OR "methyl prednisolone"[tw] OR methylcotol[tw] OR methylcotolone[tw] OR "methylpred dp"[tw] OR methylsterolone[tw] OR metidrol[tw] OR metipred[tw] OR metrisone[tw] OR metycortin[tw] OR metypred[tw] OR metypresol[tw] OR neomedrone[tw] OR nsc 19987[tw] OR nsc19987[tw] OR prednol[tw] OR solomet[tw] OR "solu decortin"[tw] OR urbason[tw] OR "6923‐42‐8"[tw] OR "83‐43‐2"[tw]
 16. Hydrocortisone[tw] OR acticort[tw] OR "aeroseb hc"[tw] OR "ala‐cort"[tw] OR "ala‐scalp"[tw] OR alfacort[tw] OR algicortis[tw] OR alkindi[tw] OR "alpha derm"[tw] OR alphaderm[tw] OR "anucort‐hc"[tw] OR "anumed‐hc"[tw] OR "anutone‐hc"[tw] OR "aquanil hc"[tw] OR "balneol‐hc"[tw] OR "barseb hc"[tw] OR "beta‐hc"[tw] OR biacort[tw] OR cetacort[tw] OR cobadex[tw] OR colocort[tw] OR "compound f"[tw] OR "cordicare lotion"[tw] OR coripen[tw] OR "cort dome"[tw] OR cortef[tw] OR cortenema[tw] OR cortibel[tw] OR corticorenol[tw] OR cortifair[tw] OR cortifan[tw] OR cortiphate[tw] OR cortisol[tw] OR cortisole[tw] OR cortispray[tw] OR cortoderm[tw] OR cortril[tw] OR cotacort[tw] OR covocort[tw] OR "cremicort‐h"[tw] OR cutaderm[tw] OR "derm‐aid cream"[tw] OR "dermacrin hc lotion"[tw] OR dermaid[tw] OR dermocare[tw] OR dermocortal[tw] OR dermolate[tw] OR dioderm[tw] OR eczacort[tw] OR "ef cortelan"[tw] OR efcortelan[tw] OR egocort[tw] OR eksalb[tw] OR eldecort[tw] OR "emo‐cort"[tw] OR epicort[tw] OR epicortisol[tw] OR ficortril[tw] OR filocot[tw] OR flexicort[tw] OR "gly‐cort"[tw] OR glycort[tw] OR "h‐cort"[tw] OR "hc no. 1"[tw] OR "hc no. 4"[tw] OR hebcort[tw] OR "hemorrhoidal hc"[tw] OR "hemril‐30"[tw] OR "hemril‐hc uniserts"[tw] OR "hi‐cor"[tw] OR hidrotisona[tw] OR hycor[tw] OR hycort[tw] OR hydracort[tw] OR hydrasson[tw] OR "hydro ricortex"[tw] OR "hydro‐rx"[tw] OR hydrocort[tw] OR hydrocorticosteroid[tw] OR hydrocortisate[tw] OR hydrocortison[tw] OR hydrocortisonum[tw] OR hydrocortisyl[tw] OR hydrocortone[tw] OR hydrogalen[tw] OR hydrokort[tw] OR hydrokortison[tw] OR hydrotopic[tw] OR hysone[tw] OR hytisone[tw] OR hytone[tw] OR "incortin h"[tw] OR "instacort 10"[tw] OR kyypakkaus[tw] OR "lacticare hc"[tw] OR "lemnis fatty cream hc"[tw] OR lenirit[tw] OR "medihaler cort"[tw] OR "medihaler duo"[tw] OR medrocil[tw] OR mildison[tw] OR "mitocortyl demangeaisons"[tw] OR munitren[tw] OR "nogenic hc"[tw] OR novohydrocort[tw] OR "nsc 10483"[tw] OR "nsc 741"[tw] OR nsc10483[tw] OR nutracort[tw] OR optef[tw] OR "otosone f"[tw] OR penecort[tw] OR plenadren[tw] OR prepcort[tw] OR "prevex hc"[tw] OR "pro cort"[tw] OR procort[tw] OR "procto‐kit"[tw] OR proctocort[tw] OR "proctosert hc"[tw] OR "proctosol‐hc"[tw] OR proctosone[tw] OR "proctozone hc"[tw] OR procutan[tw] OR "rectasol‐hc"[tw] OR rectocort[tw] OR rederm[tw] OR sanatison[tw] OR "scalp‐aid"[tw] OR schericur[tw] OR "scherosone f"[tw] OR skincalm[tw] OR "stie‐cort"[tw] OR "substance m"[tw] OR synacort[tw] OR texacort[tw] OR "triburon‐hc"[tw] OR unicort[tw] OR vasocort[tw] OR "50‐23‐7"[tw]
 17. Loteprednol[tw] OR alrex[tw] OR "cddd 5604"[tw] OR cddd5604[tw] OR CEHOAC[tw] OR "chloromethyl 17alpha ethoxycarbonyloxy 11beta hydroxy 3 oxoandrosta 1, 4 diene 17 carboxylate"[tw] OR "hgp 1"[tw] OR hgp1[tw] OR inveltys[tw] OR "kpi 121"[tw] OR kpi121[tw] OR "le‐mpp"[tw] OR lotemax[tw] OR loterex[tw] OR loterox[tw] OR lotesoft[tw] OR "p 5604"[tw] OR p5604[tw] OR "82034‐46‐6"[tw]
 18. Rimexolone[tw] OR baxol[tw] OR "org 6216"[tw] OR org6216[tw] OR "pregna 1, 4 dien 11beta ol 3, 20 dione, 16alpha, 17alpha, 21 trimethyl"[tw] OR rimexel[tw] OR trimexolone[tw] OR vexol[tw] OR vexolon[tw] OR "49697‐38‐3"[tw]
 19. "Prednisolone acetate"[tw] OR "ak‐pred"[tw] OR deppredalone[tw] OR econopred[tw] OR "flo pred"[tw] OR "isopto cetapred"[tw] OR "key pred"[tw] OR "meticortelone acetate"[tw] OR "ocu‐pred"[tw] OR omnipred[tw] OR optilon[tw] OR "poly pred"[tw] OR "pred forte"[tw] OR "pred mild"[tw] OR predforte[tw] OR predmet[tw] OR "prednefrin sf"[tw] OR "predni h"[tw] OR "predni‐ophtal"[tw] OR prednigalen[tw] OR "prednisolone 17 acetate"[tw] OR "prednisolone 21 acetate"[tw] OR "prednisolone acetate suspension"[tw] OR savacort[tw] OR "Scherisolone‐Kristall suspension"[tw] OR ultracortensol[tw] OR ultracortinol[tw] OR "52‐21‐1"[tw] OR "52628‐64‐5"[tw]
 20. Beclomethasone[tw] OR beclometasone[tw] OR "Asmabec Clickhaler"[tw] OR Ascocortonyl[tw] OR Beclamet[tw] OR "Beclo Asma"[tw] OR "Beclo AZU"[tw] OR Beclocort[tw] OR Beclomet[tw] OR "Bemedrex Easyhaler"[tw] OR Beclorhinol[tw] OR Sanasthmax[tw] OR Becloturmant[tw] OR Beclovent[tw] OR Beconase[tw] OR Becloforte[tw] OR Becodisk[tw] OR Becodisks[tw] OR Propaderm[tw] OR Becotide[tw] OR Sanasthmyl[tw] OR "Beconase AQ"[tw] OR Bronchocort[tw] OR Junik[tw] OR Qvar[tw] OR Ecobec[tw] OR Beclazone[tw] OR Ventolair[tw] OR Prolair[tw] OR Filair[tw] OR "AeroBec Forte"[tw] OR Aerobec[tw] OR "Nasobec Aqueous"[tw] OR Respocort[tw] OR Vancenase[tw] OR Vanceril[tw] OR Aldecin[tw] OR Viarin[tw] OR "4419‐39‐0"[tw]
 21. Betamethasone[tw] OR adbeon[tw] OR becasone[tw] OR beprogel[tw] OR "beta methason"[tw] OR "beta methasone"[tw] OR "beta‐phos/ac"[tw] OR betacortril[tw] OR betadexamethasone[tw] OR betametasone[tw] OR betamethasolone[tw] OR betamethason[tw] OR betamethasonium[tw] OR betamethasonum[tw] OR betamethazone[tw] OR betason[tw] OR betnasol[tw] OR betnelan[tw] OR "betnesol h"[tw] OR "betnesol v"[tw] OR "betnovate a"[tw] OR betsolan[tw] OR betsolon[tw] OR betsopart[tw] OR celestan[tw] OR celestene[tw] OR celeston[tw] OR celestona[tw] OR celestone[tw] OR cellestoderm[tw] OR cidoten[tw] OR dermobet[tw] OR diprolen[tw] OR flubenisolone[tw] OR methasone[tw] OR "nsc 39470"[tw] OR nsc39470[tw] OR "pregna 1, 4 diene 3, 20 dione 11, 17, 21 triol, 9 alpha fluoro 16beta methyl"[tw] OR "rg 833"[tw] OR rg833[tw] OR rinderon[tw] OR "sch 4831"[tw] OR sch4831[tw] OR walacort[tw] OR "378‐44‐9"[tw]
 22. Budesonide[tw] OR acorspray[tw] OR aerox[tw] OR allercort[tw] OR aquacort[tw] OR "b cort"[tw] OR "bebe cream"[tw] OR bidien[tw] OR budecol[tw] OR budecort[tw] OR budefat[tw] OR budeflam[tw] OR budelin[tw] OR "budenase aq"[tw] OR budeno[tw] OR budenofalk[tw] OR budenoside[tw] OR budes[tw] OR budeson[tw] OR "budesonide easyhaler"[tw] OR budiair[tw] OR "budicort respules"[tw] OR "budo‐san"[tw] OR budon[tw] OR budosan[tw] OR bunase[tw] OR buparid[tw] OR butacort[tw] OR clebudan[tw] OR coramen[tw] OR cortiment[tw] OR cortimentmmx[tw] OR cycortide[tw] OR "desona nasal"[tw] OR desonix[tw] OR dexbudesonide[tw] OR duasma[tw] OR eltair[tw] OR entocir[tw] OR entocort[tw] OR esonide[tw] OR "giona easyhaler"[tw] OR horacort[tw] OR inflammide[tw] OR inflanaze[tw] OR intesticort[tw] OR intestifalk[tw] OR jorveza[tw] OR larbex[tw] OR "map 0010"[tw] OR map0010[tw] OR miflo[tw] OR miflonid[tw] OR miflonide[tw] OR miflonil[tw] OR mikicort[tw] OR nebbud[tw] OR "neo‐rinactive"[tw] OR novopulmon[tw] OR numark[tw] OR olfex[tw] OR preferid[tw] OR "pregna 1, 4 diene 3, 20 dione 16, 17 butyraldehyde cyclic acetal, 11beta, 16alpha, 17, 21 tetrahydroxy"[tw] OR pulmaxan[tw] OR "pulmicon susp for nebulizer"[tw] OR "pulmicon susp for nebulizer"[tw] OR pulmicort[tw] OR pulmoliseflam[tw] OR pulmotide[tw] OR respicort[tw] OR rhinocort[tw] OR ribujet[tw] OR ribuspir[tw] OR ribuvent[tw] OR "s 1320"[tw] OR s1320[tw] OR spirocort[tw] OR "tafen nasal"[tw] OR uceris[tw] OR "51333‐22‐3"[tw] OR "51372‐29‐3"[tw]
 23. Ciclesonide[tw] OR alvesco[tw] OR "b 9207 015"[tw] OR "b 9207015"[tw] OR "b9207 015"[tw] OR "b9207015"[tw] OR "by 9010"[tw] OR "by9010"[tw] OR omnaris[tw] OR zetonna[tw] OR "126544‐47‐6"[tw]
 24. Flunisolide[tw] OR aerobid[tw] OR aerospan[tw] OR bronalide[tw] OR bronilide[tw] OR cyntaris[tw] OR flunitec[tw] OR gibiflu[tw] OR inhacort[tw] OR locasyn[tw] OR lokilan[tw] OR "lunibron‐a"[tw] OR lunis[tw] OR nasalide[tw] OR nasarel[tw] OR rhinalar[tw] OR "rs 3999"[tw] OR rs3999[tw] OR sanergal[tw] OR synaclyn[tw] OR syntaris[tw] OR "val 679"[tw] OR val679[tw] OR "3385‐03‐3"[tw]
 25. Fluticasone[tw] OR Flonase[tw] OR Flovent[tw] OR Cutivate[tw] OR Flixonase[tw] OR Flixotide[tw] OR "90566‐53‐3"[tw]
 26. Mometasone[tw] OR "allermax aqueous"[tw] OR asmanex[tw] OR belloseta[tw] OR bloctimo[tw] OR breso[tw] OR brusonex[tw] OR cutticom[tw] OR dermotasone[tw] OR dermovel[tw] OR desdek[tw] OR ecural[tw] OR edelan[tw] OR elica[tw] OR elocom[tw] OR elocon[tw] OR elocyn[tw] OR elomet[tw] OR eloson[tw] OR flumeta[tw] OR frondava[tw] OR ivoxel[tw] OR kalmente[tw] OR lorome[tw] OR mefurosan[tw] OR metaspray[tw] OR metmin[tw] OR mipasu[tw] OR mofunder[tw] OR momate[tw] OR momeallerg[tw] OR momecutan[tw] OR momederm[tw] OR momegalen[tw] OR momekort[tw] OR momesonex[tw] OR momespir[tw] OR momester[tw] OR mometahexal[tw] OR mometason[tw] OR mometasone[tw] OR mometop[tw] OR mommox[tw] OR monovel[tw] OR monovo[tw] OR morecort[tw] OR motaderm[tw] OR mundoson[tw] OR muofuder[tw] OR nasehaler[tw] OR nasoaldo[tw] OR nasomet[tw] OR nasometin[tw] OR nasonex[tw] OR nasotasone[tw] OR netonox[tw] OR "novasone cream"[tw] OR "novasone lotion"[tw] OR "novasone ointment"[tw] OR ovison[tw] OR ovixan[tw] OR pronasal[tw] OR rinelon[tw] OR rinometasone[tw] OR rivelon[tw] OR "sch 32088"[tw] OR sch32088[tw] OR sebanez[tw] OR sinuva[tw] OR sonalox[tw] OR temon[tw] OR uniclar[tw] OR zhekort[tw] OR "105102‐22‐5"[tw] OR "83919‐23‐7"[tw]
 27. Triamcinolone[tw] OR acetocot[tw] OR adcortyl[tw] OR aristocort[tw] OR aristodan[tw] OR azmacor[tw] OR celeste[tw] OR "cl 19823"[tw] OR cl19823[tw] OR clinacort[tw] OR clinalog[tw] OR delphicort[tw] OR fluoxiprednisolone[tw] OR fluoxyprednisolone[tw] OR "ken‐jec 40"[tw] OR kenacort[tw] OR korticoid[tw] OR ledercort[tw] OR omcilon[tw] OR polcortolon[tw] OR "rp 8357"[tw] OR rp8357[tw] OR simacort[tw] OR sterocort[tw] OR "tac 3"[tw] OR tramcinolone[tw] OR triacortyl[tw] OR "triam‐a"[tw] OR "triam‐forte"[tw] OR triamcinolon[tw] OR triamcinolona[tw] OR triamcort[tw] OR triamcot[tw] OR "triamonide 40"[tw] OR triamsicort[tw] OR triancinolon[tw] OR "u‐tri‐lone"[tw] OR volon[tw] OR "124‐94‐7"[tw]
 28. #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27
 29. #8 AND #28
 30. #1 AND #29
 31. Medline[sb]
 32. #30 NOT #31

Appendix 5. LILACS search strategy

(MH:C01.539.800.130$ OR MH:C01.539.830.200$ OR MH:C17.300.185$ OR MH:C23.550.470.756.200$ OR MH:C11.675.387$ OR MH:C01.252.354$ OR MH:C01.539.375.354$ OR MH:C11.294.354 OR MH:C11.675 OR MH:C08.460.692.752$ OR MH:C08.730.749$ OR MH:C09.603.692.752$ OR (periorbit$ celluliti$) OR (orbit$ celluliti$) OR (preseptal celluliti$) OR ("pre septal" celluliti$) OR (postseptal celluliti$) OR ("post septal" celluliti$) OR (subperiosteal abscess$) OR ("sub periosteal" abscess$) OR (orbital abscess$) OR (intraconal abscess$) OR (Bacterial eye infect$) OR (orbital disease$) OR sinusitis OR (sinus infect$) OR rhinosinusitis OR "Sinus venous thrombosis") AND ((mh:("Orbital Cellulitis/DT")) OR MH:D04.210.500$ OR steroid$ OR MH:D06.472.040$ OR ("Adrenal Cortex" Hormone$) OR Corticosteroid$ OR Corticoid$ OR Glucocorticoid$ OR (Glucorticoid Effect$) OR Hydroxycorticosteroid$ OR ("Adrenal cortical" hormone$) OR (Adrenocortical hormone$) OR Adrenocorticosteroid$ OR Dermocorticosteroid$ OR Glucocorticosteroid$ OR Glucocorticoidsteroid$ OR Glucocortoid$ OR Glycocorticoid$ OR Glycocorticosteroid$ OR Dexamethasone OR Prednisone OR Prednisolone OR Methylprednisolone OR Hydrocortisone OR Loteprednol OR Rimexolone OR Beclomethasone OR Betamethasone OR Budesonide OR Ciclesonide OR Flunisolide OR Fluticasone OR Mometasone OR Triamcinolone)

Appendix 6. ClinicalTrials.gov search strategy

(Cellulitis OR subperiosteal abscess OR sub periosteal abscess OR orbital abscess OR intraconal abscess OR bacterial eye infection OR orbital disease OR sinusitis OR rhinosinusitis OR Sinus venous thrombosis) AND (steroid OR Adrenal Cortex Hormones OR Corticosteroid OR Corticoid OR Glucocorticoid OR Glucorticoid Effect OR Hydroxycorticosteroid OR Adrenal cortical hormone OR Adrenocortical hormone OR Adrenocorticosteroid OR Dermocorticosteroid OR Glucocorticosteroid OR Glucocorticoidsteroid OR Glucocortoid OR Glycocorticoid OR Glycocorticosteroid OR Dexamethasone OR Prednisone OR Prednisolone OR Methylprednisolone OR Hydrocortisone OR Loteprednol OR Rimexolone OR Beclomethasone OR Betamethasone OR Budesonide OR Ciclesonide OR Flunisolide OR Fluticasone OR Mometasone OR Triamcinolone)

Appendix 7. WHO ICTRP search strategy

Cellulitis AND steroid OR Cellulitis AND Adrenal Cortex Hormones OR Cellulitis AND Corticosteroid OR Cellulitis AND Corticoid OR Cellulitis AND Glucocorticoid OR Cellulitis AND Glucorticoid Effect OR Cellulitis AND Hydroxycorticosteroid OR Cellulitis AND Adrenal cortical hormone OR Cellulitis AND Adrenocortical hormone OR Cellulitis AND Adrenocorticosteroid OR Cellulitis AND Dermocorticosteroid OR Cellulitis AND Glucocorticosteroid OR Cellulitis AND Glucocorticoidsteroid OR Cellulitis AND Glucocortoid OR Cellulitis AND Glycocorticoid OR Cellulitis AND Glycocorticosteroid OR Cellulitis AND Dexamethasone OR Cellulitis AND Prednisone OR Cellulitis AND Prednisolone OR Cellulitis AND Methylprednisolone OR Cellulitis AND Hydrocortisone OR Cellulitis AND Loteprednol OR Cellulitis AND Rimexolone OR Cellulitis AND Beclomethasone OR Cellulitis AND Betamethasone OR Cellulitis AND Budesonide OR Cellulitis AND Ciclesonide OR Cellulitis AND Flunisolide OR Cellulitis AND Fluticasone OR Cellulitis AND Mometasone OR Cellulitis AND Triamcinolone

Appendix 8. Data on study characteristics

Mandatory items		Optional items
Methods
Study design	· Parallel group RCTi.e. people randomized to treatment · Within‐person RCTi.e. eyes randomized to treatment · Cluster RCTi.e. communities randomized to treatment · Cross‐over RCT · Other, specify	Exclusions after randomization Losses to follow‐up Number randomized/analyzed How were missing data handled? e.g., available case analysis, imputation methods Reported power calculation (Y/N), if yes, sample size and power Unusual study design/issues
Eyes or Unit of randomization/ unit of analysis	· One eye included in study, specify how eye selected · Two eyes included in study, both eyes received same treatment, briefly specify how analyzed(best/worst/average/both and adjusted for within person correlation/both and not adjusted for within person correlation) and specify if mixture one eye and two eyes · Two eyes included in study, eyes received different treatments,specify if correct pair‐matched analysis done
Participants
Country		Setting Ethnic group Equivalence of baseline characteristics (Y/N)
Total number of participants	This information should be collected for total study population recruited into the study. If these data are only reported for the people who were followed up only, please indicate.
Number (%) of men and women
Average age and age range
Inclusion criteria
Exclusion criteria
Interventions
Intervention (n= ) Comparator (n= ) See MECIR 65 and 70	· Number of people randomized to this group · Drug (or intervention) name · Dose · Frequency · Route of administration
Outcomes
Primary and secondary outcomes as defined in study reports See MECIR R70	List outcomes Adverse events reported (Y/N) Length of follow‐up and intervals at which outcomes assessed	Planned/actual length of follow‐up

Contributions of authors

PG: conceived, designed,drafted the protocol, and reviewed subsequent revisions.
 PP: conceived, reviewed protocol in detail, and commented on it critically for intellectual content.
 YAR: reviewed protocol in detail and commented on it critically for intellectual content, particularly relating to outcome measurement.
 SS: reviewed protocol in detail and commented on it critically for intellectual content.
 EK: reviewed protocol in detail, and commented on it critically for intellectual content.
 SM: conceived, reviewed protocol in detail, and commented on it critically for intellectual content.

All authors reviewed and approved the protocol.

Sources of support

Internal sources

• Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

  Pediatric Research and Clinical Summer (PeRCS) Program at Hospital for Sick Children.

• Paediatric Outcomes Research Team (PORT), Canada.

  Hospital for Sick Children Foundation

External sources

• Cochrane Eyes and Vision Group US Project, supported by grant 1 U01 EY020522‐01, National Eye Institute, National Institutes of Health, USA.

• National Institute for Health Research (NIHR), UK.

  • Richard Wormald, Co‐ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the NIHR to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.
  • This protocol was supported by the NIHR, via Cochrane Infrastructure funding to the CEV UK editorial base.

  The views expressed in this publication are those of the review authors and not necessarily those of the NIHR, the NHS, or the Department of Health.

Declarations of interest

PG: none.
 PP: none.
 YAR: none.
 SS: none.
 EK: none.
 SM: none.

New