Pharmacologic interventions for mydriasis in cataract surgery

Abstract

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

Primary objectives

To evaluate the effectiveness of various methods of pupillary dilation among people who underwent phacoemulsification for cataract extraction. Comparisons of interest include topical mydriatics versus intracameral mydriatics, topical mydriatics versus depot delivery systems, and intracameral mydriatics versus depot delivery systems.

Secondary objectives

To assess and compare the incidence of intra‐ and postoperative cardiovascular and ocular complications associated with the use of these methods of pupillary dilation. We will also compare the cost‐effectiveness of these methods during routine cataract surgery.

Background

Description of the condition

Cataract is the most common correctable cause of visual impairment worldwide. It is defined as any opacity within the naturally clear lens inside the eye. The presence of this opacity is associated with increased scattering of light and decreased image contrast sensitivity (Adamsons 1992; Shandiz 2011). Visual acuity is often preserved initially, and those affected more commonly complain of glare or difficulty with night driving. Other symptoms include light sensitivity, seeing halos around lights, monocular double vision, and seeing colors less bright.

An estimated 150 million individuals suffered from cataract‐related visual impairment in 2010, and 10 million cataract operations are done each year, although the need is estimated to be at least 30 million per year (Foster 2001). It is estimated that over the next 20 years the burden will increase by about one‐third, predominantly in low‐ and middle‐income countries. Its economic impact is still substantial in high‐income countries. In the United States alone, over 20 million people were affected by cataracts, and approximately 3 million surgeries are performed annually at a cost of $3.4 billion to Centers for Medicare and Medicaid Services (Congdon 2004; Klein 2013).

Cataract formation is a multifactorial process. Risk factors include age, gender, smoking, alcohol use, ultraviolet radiation exposure, diabetes, nutritional factors, and certain medications (e.g. steroids) (Prokofyeva 2013). In particular, increasing age has a strong association. The prevalence of cataract in Europe increased from 5% for those 52 to 62 years of age to 30% and 64% for those 60 to 69 years of age and 70 years and above, respectively (Das 1994; Navarro Esteban 2007). At present, surgery remains the only definitive treatment, and no therapy exists for its prevention.

Description of the intervention

Cataract surgery is one of the oldest known surgical procedures (Spalton 2000), and has evolved to be one of the safest and most commonly performed surgical procedures worldwide, with significantly improved visual outcomes and faster recovery times. Intracapsular cataract extraction (ICCE) followed by extracapsular extraction (ECCE) were the initial procedures of choice, routinely undertaken until the 1960s. The most significant development in cataract surgery was the introduction of phacoemulsification in 1967, followed by intraocular lens (IOL) implantation, considered now to be the gold standard technique (Kelman 1994; Linebarger 1999).

Achieving appropriate mydriasis intraoperatively is one of the critical factors associated with ease of performing the surgery and its safety (Grob 2014; Saenz‐de‐Viteri 2013), as most surgical steps except for the clear cornea incision are performed at or behind the plane of the iris (Ho 1992). High‐risk groups showing poor pupillary dilation include people with pseudoexfoliation syndrome (Sangal 2014), diabetes mellitus (Smith 1983), posterior synechiae, eye trauma, and those taking alpha‐adrenergic receptor agonists (Manvikar 2006). Inadequate pupillary dilation or constriction of the pupil during cataract surgery reduces the surgeon’s field of view, can make maneuvering of instruments difficult, and is a known risk factor for various intraoperative complications such as iris prolapse and damage, incomplete cortex removal, posterior capsule rupture, dropped nucleus of the lens, vitreous loss, cystoid macular edema, and retinal detachment (Chen 2014; Goodman 1989; Hashemi 2013). Adequate pupillary dilation is essential for safe completion of cataract surgery and for reducing the incidence of complications.

Mydriatic agents can be administered traditionally via topical eye drops or through alternative methods such as intracameral mydriasis and depot delivery systems (Mydriasert/sponge).

How the intervention might work

Topical mydriatic agents (phenylephrine, cyclopentolate, and/or tropicamide) typically have sympathomimetic or anticholinergic properties, or both, and are frequently administered before and during cataract surgery to maintain adequate pupillary dilation. However, this regimen has significant limitations. These topical agents have a low penetration into the eye (2% to 10%), with most of the drug being systemically absorbed (Salminen 1990). Due to the slow penetration, maximum onset of dilation takes at least 30 minutes, which can be longer than the time of the cataract surgery; furthermore, the dilation can wear off during the surgery (Liou 2009; Lundberg 2003). There is also a risk of cardiovascular complications (i.e. increase in blood pressure and heart rate) associated with their use, especially in people who have a history of hypertension or underlying cardiac disease (Diamond 1997; Hakim 1990). In addition, frequent spillage of the drop from the palpebral fissure makes successful administration of topical mydriatics difficult in some patients.

Intracameral mydriasis involves the injection of a mydriatic directly into the anterior chamber after the initial incision into the eye (Lundberg 2008; Lundberg 2009). This method usually requires lesser concentrations of mydriatics as compared with standard topical doses (Lundberg 2003), and has been shown to significantly decrease the risk of systemic adrenergic side effects including cardiovascular complications (Fraunfelder 1985; Morgado 2010).

Mydriasert is a long‐acting drug insert (0.28 mg tropicamide and 5.4 mg phenylephrine hydrochloride) with greater bioavailability than topical mydriatic agents and increased local efficacy and decreased systemic absorption (Saenz‐de‐Viteri 2013). The risk of systemic complications is therefore less with Mydriasert, and it can serve as a safe and effective alternative to topical mydriatics. Unlike topical drops, which require frequent administration, Mydriasert is usually applied to the inferior fornix 60 minutes before surgery, and hence might be a simpler and more effective alternative. However, despite these advantages, the use of this insert is limited due to doubts regarding the best time for its insertion and its ability to maintain mydriasis long enough during cataract surgery, as well as the cost (Saenz‐de‐Viteri 2013). The pledget mode of delivery of topical mydriatics agents is another convenient and time‐saving option.

Why it is important to do this review

Topical mydriatic drops have traditionally been used for pupillary dilation during cataract surgery. Intracameral administration of mydriatics and depot mydriatic delivery systems (Mydriasert/sponge) are reasonable alternatives. The most effective intervention for achieving adequate intraoperative mydriasis during cataract surgery has not yet been established. This review will help answer this question by comparing the effectiveness and safety profile of topical mydriatics, intracameral delivery of mydriatics, and depot delivery systems.

Objectives

Primary objectives

To evaluate the effectiveness of various methods of pupillary dilation among people who underwent phacoemulsification for cataract extraction. Comparisons of interest include topical mydriatics versus intracameral mydriatics, topical mydriatics versus depot delivery systems, and intracameral mydriatics versus depot delivery systems.

Secondary objectives

To assess and compare the incidence of intra‐ and postoperative cardiovascular and ocular complications associated with the use of these methods of pupillary dilation. We will also compare the cost‐effectiveness of these methods during routine cataract surgery.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomized controlled trials only.

Types of participants

We will include trials in which participants underwent phacoemulsification for cataract extraction, excluding studies of femtosecond‐assisted cataract surgery. We will use no age or gender restriction.

Types of interventions

We will include trials comparing the effectiveness and safety of two or more of the following interventions: topical mydriatics versus intracameral mydriatics versus depot delivery systems. The specific comparisons of interest are:

1. topical mydriatics versus intracameral mydriatics;

2. topical mydriatics versus depot delivery systems;

3. intracameral mydriatics versus depot delivery systems.

We will not include dosing studies in which no active comparison group was included. We will not include studies that compared only one type of mydriatic agent with placebo.

Types of outcome measures

Primary outcomes

The primary outcome for this review will be the mean pupillary diameter (mm) at the time the surgeon performs capsulorhexis, measured using a pupillometer, surgical caliper, or comparable device or measurements registered from digital video recordings of the procedure. We also will assess the mean pupillary diameter at the beginning of the procedure and at the end of the procedure when data are available.

Secondary outcomes

1. The total intraoperative surgical time, from when the initial incision was made to the end of the procedure when the surgery was complete and the eye patched after each intervention.

2. The total time it took for the surgeon to perform phacoemulsification after each intervention

3. Participant‐reported ocular discomfort after each intervention at any time point during or after the surgery.

Adverse events

We will compare intraoperative complications including iris prolapse and damage, incomplete cortex removal, posterior capsule rupture, dropped nucleus, vitreous loss, cystoid macular edema, and retinal detachment.

We also will investigate the proportion of participants with cardiovascular complications other than increase in blood pressure and heart rate, pre‐, intra‐, and postoperatively.

Economic outcomes

We will compare cost outcomes as reported in the included trials, namely whether the use of one mydriatic intervention has a significant benefit over the others in primary and secondary outcome measures as well as cost‐effectiveness that would warrant its use in clinical practice.

Search methods for identification of studies

Electronic searches

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

• 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 reference lists of included publications in order to identify any additional studies. We will use the Web of Science Citation Index to find studies that have cited the included trials. We will not search conference proceedings specifically for this review because conference proceedings from relevant ophthalmology meetings are searched annually by Cochrane Eyes and Vision and identified randomized controlled trials are included in the CENTRAL database.

Data collection and analysis

Selection of studies

Two review authors will independently screen titles and abstracts retrieved from the searches. We will classify each record as relevant, potentially relevant, or definitely not relevant and retrieve full‐text reports of records classified as relevant or potentially relevant. Two review authors will independently screen each full‐text report to determine eligibility for inclusion in the review and classify each report as eligible for inclusion, excluded, or assessed as awaiting classification. We will document studies excluded at this stage and report the reasons for exclusion. We will contact study authors of studies assessed as awaiting classification in an attempt to obtain information needed to either include or exclude the study from the review. Study authors will have two weeks to respond. At that time we will classify the study based on the available information.

Disagreements between the two review authors will be resolved by discussion or by arbitration from a third review author if needed. We will not mask the names of the authors, institutions, or journals when reviewing studies.

Data extraction and management

Two review authors will independently extract data from the included trials using a standard data extraction form. We will extract data related to study characteristics (Appendix 8), study methods, and outcomes. Any discrepancies and disagreements will be resolved through discussion or by arbitration from a third review author if needed. We will contact trial authors for missing or unclear data and provide them two weeks to respond. If we do not receive a response within two weeks, we will report and assess the study using the available data. One review author will enter the data into Review Manager 5 (Review Manager 5 2014), and a second review author will check the data for inaccuracies.

Assessment of risk of bias in included studies

Two review authors will independently assess the included trials for risk of bias. We will assess the following domains for each included trial as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a).

• Selection bias: sequence generation and allocation concealment

• Performance bias: masking of participants and personnel

• Detection bias: masking of outcome assessment

• Attrition bias: incomplete outcome data

• Reporting bias: selective outcome reporting. If the protocol or clinical trial registry record for the included trial is available, we will evaluate the study for evidence of systematic differences between reported and unreported findings.

We will assess each 'Risk of bias' domain as low, high, or unclear and provide descriptions as to our reasoning for such assessments. Disagreements will be resolved by discussion or by consulting a third review author when necessary.

Measures of treatment effect

We will calculate mean differences with 95% confidence intervals for outcome measures reported as continuous data (the measurement of the pupillary diameter (mm) at various time points, total intraoperative surgical time, total time to perform phacoemulsification, the direct, indirect, and total costs associated with each intervention). We will calculate risk ratios with 95% confidence intervals for outcome measures reported as dichotomous data (the proportion of participants with adverse events and participant‐reported ocular discomfort).

Unit of analysis issues

We expect that most of the included trials will have randomized a single eye per participant to a single intervention. We will also consider the participant as the unit analysis when both eyes of a single participant were randomized and analyzed as a unit. In the case where both eyes of participants were included and analyzed with the eye as the unit of analysis, we will attempt to analyze the data adjusting for clustering or paired‐eye design as appropriate and as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b).

Dealing with missing data

In the case of missing data we will contact authors to try to obtain these data. If such attempts are unsuccessful, we will perform the analysis using the available data. We will not impute data for the purposes of this review.

Assessment of heterogeneity

We will assess for clinical, methodological, and statistical heterogeneity among included studies. When no substantial clinical or methodological heterogeneity is identified, we will combine studies in meta‐analysis. We will look at the consistency across studies by examining the value of the I² statistic, the direction of effects, and the overlap of confidence intervals on the forest plot. We will consider I² values greater than 60% to represent substantial statistical heterogeneity. Differences in the direction of effects and poor overlap of confidence intervals among studies also suggest heterogeneity among studies.

Assessment of reporting biases

We will assess publication bias with the funnel plot and Egger’s regression intercept when 10 or more studies are included in a meta‐analysis. We will assess for potential selective outcome reporting by study as part of the 'Risk of bias' assessment.

Data synthesis

When data are sufficient and no substantial clinical, methodological, and statistical heterogeneity are identified, we will conduct meta‐analysis using a random‐effects model. If fewer than three studies are included in a meta‐analysis, we will use a fixed‐effect model. If we determine that conducting a meta‐analysis is inappropriate due to heterogeneity, we will report a narrative or tabulated summary. We will use a 95% confidence interval throughout.

Subgroup analysis and investigation of heterogeneity

When sufficient data are available, we will undertake the following a priori defined subgroup analyses.

1. Participants using alpha‐adrenergic agonists

2. Participants with pseudoexfoliation syndrome

3. Participants with diabetes mellitus

4. Participants with pre‐existing cardiac conditions

5. Participants receiving preoperative and intraoperative non‐steroidal anti‐inflammatory drugs

We will analyze whether the treatment effect differs for these subgroups and assess the overlap in confidence intervals.

Sensitivity analysis

We will conduct the following sensitivity analyses when sufficient data are available:

1. excluding trials assessed as being at high risk of bias for the allocation concealment or masking domains;

2. excluding studies that are industry funded; and

3. excluding studies that have not been published as a full‐length report.

Summary of findings

When there is sufficient evidence to merit the preparation of a 'Summary of findings' table, we will develop a table for the main outcomes for each comparison (topical mydriatics versus intracameral mydriatics, topical mydriatics versus depot delivery systems, and intracameral mydriatics versus depot delivery systems). The seven main outcomes for this review are as follows.

1. Mean pupillary diameter (mm) at the beginning of the procedure

2. Mean pupillary diameter (mm) before capsulorhexis

3. Mean pupillary diameter (mm) at the end of the procedure

4. Total intraoperative surgical time

5. Total time to perform phacoemulsification

6. Participant‐reported ocular discomfort after each intervention at any time point during or after the surgery

7. Proportion of participants with adverse events

We will assess the quality of the evidence using the GRADE approach (GRADEpro 2014), grading the evidence for each outcome as high, moderate, low, or very low according to the following criteria as described in Chapter 12 of the Cochrane Handbook for Systematic Reviews of Interventions (Schünemann 2011).

• High risk of bias among included studies

• Indirectness of evidence

• Unexplained heterogeneity or inconsistency of results

• Imprecision of results (i.e. wide confidence intervals)

• High probability of publication bias

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Cataract] explode all trees #2 MeSH descriptor: [Cataract Extraction] explode all trees #3 (extract* or aspirat* or operat* or remov* or surg* or excis* or implant*) near/4 (cataract*) #4 (extract* or aspirat* or operat* or remov* or surg* or excis* or implant* or emulsif*) near/4 (lens*) #5 phakectom* or lensectom* or zonulolys* or catarectom* #6 pha?oemulsif* or (pha?o next/1 emulsif*) or facoemulsif* or (faco next/1 emulsif*) #7 Capsulorhexis or Capsulorrhexis #8 {or #1‐#7} #9 MeSH descriptor: [Mydriasis] explode all trees #10 MeSH descriptor: [Miotics] explode all trees #11 MeSH descriptor: [Miosis] explode all trees #12 Miotic* or Miosis or myosis or mydriasis or Mydriasert or (pupil* near/3 dilat*) #13 MeSH descriptor: [Mydriatics] explode all trees #14 mydriatic* #15 cycloplegic* #16 MeSH descriptor: [Atropine] explode all trees #17 Atropine or atrinal or "atro‐polygyl" or atrop or atropen or atropin or atropina or "atropini sulfas" or atropinol or atropisol or atropt or atroptol or atrospan or "atrosulf‐1" or "bar bropin" or "bellpino‐artin" or "cendo tropine" or "dextro levo hyosciamine" or "ichtho bellol" or "isopto" or isoptoAtropine or "ocu‐tropine" or "sal‐tropine" or skiatropine or "tropine dextro levo tropate" or ximex or "51‐55‐8" or "55‐48‐1" #18 berefrine or POPD or "105567‐83‐7" #19 MeSH descriptor: [Cyclopentolate] explode all trees #20 Cyclopentolate or "ak‐pentolate" or akpentolate or "bell pentolate" or ciclolux or cyclogyl or cyclomydri or cyclopentol or cyclopentolat or cylate or cyplegin or diopentolate or midriodavi or mydrilate or "ocu‐pentolate" or ocucyclo or "oftan‐syklo" or pentolair or "refractyl ofeno" or skiacol or zyklolat or "512‐15‐2" or "5870‐29‐1" #21 MeSH descriptor: [Epinephrine] explode all trees #22 Epinephrine or Adrenaline or adrenalin or Epitrate or Lyophrin or Epifrin or adnephrin or adnephrine or adrenaclick or "adrenal hydrochloride" or adrenalina or adrenamine or adrenapax or adrenazin or adrenine or adrin or adrine or advaradin or balmadren or biorenine or bosmin or chelafrin or dylephrin or epiglaufrin or epimephrine or epinefrina or epinephran or epinephrin or epirenamine or epirenan or exadrin or glaucon or glaucosan or glaufrin or "glin epin" or glycirenan or haemostatin or hemisine or hemostasin or hemostatin or hypernephrin or "isopto epinal" or levoadrenalin or levoadrenaline or levoepinephrine or levorenin or levorenine or methylaminoethanolcatechol or methylarterenol or mucidrina or myosthenine or "n methylnoradrenalin" or nephridine or nieraline or paranephrin or posumin or renaglandin or renaglandulin or renaleptine or renalina or renaline or renoform or renostypticin or renostyptin or scurenaline or simplene or soladren or sphygmogenin or styptirenal or supracapsulin or supranephrane or supranephrin or supranol or suprarenaline or suprarenin or suprarenine or suprel or surenine or surrenine or "sus‐phrine sulfite‐free" or susphrine or "sympathin I" or takamina or tonogen or vasoconstrictine or vasodrine or vasotonin or weradren or "51‐43‐4" or "55‐31‐2" or "6912‐68‐1" #23 MeSH descriptor: [Ethylmorphine] explode all trees #24 Ethylmorphine or Ethomorphine or Trachyl or codethyline or diolan or dionine or "ethyl morphine" or ethylmorfine or ethylmorphin or "morphine ethyl ether" or "125‐30‐4" or "76‐58‐4" #25 Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6" #26 Homatropine or homatro or homatrocil or homatropaire or homatropin or homatropina or isoptoHomatropine or "I Homatrine" or "mandelyl tropeine" or mandelyltropeine or "mydryn eye" or "omatropina lux" or "tropine mandelate" or "51‐56‐9" or "87‐00‐3" #27 MeSH descriptor: [Hyoscyamine] explode all trees #28 Hyoscyamine or anaspaz or cystospaz or cytospaz or daturine or donnamar or duboisine or egacen or hyoscamine or hyosciamine or hyoscyanin or hyosyne or "ib‐stat" or levbid or levsin or "levsinex sr" or neosol or nulev or spasdel or "symax sl" or "symax sr" or "tropine l tropate" or "101‐31‐5" or "306‐03‐6" #29 Ibopamine or "N‐methyldopamine diisobutyrate" or "SB 7505" or "SB7505" or Escandine or Inopamil or "diisobutyric n methyldopamine ester" or scandine or "skf 100168" or "skf 100168 a" or "66195‐31‐1" or "75011‐65‐3" #30 Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4" #31 MeSH descriptor: [Naphazoline] explode all trees #32 Naphazoline or "Afazol Grin" or "AK Con" or AKCon or Albalon or albasol or "All Clear" or allersol or antan or benil or cefasan or "Clear Eyes" or coldan or "Colirio Alfa" or "comfort eye drops" or dazolin or "degest 2" or derinox or Idril or imidin or minha or Miraclar or mirafrin or Nafazair or nafazoline or naftazolina or "naphacel ofteno" or naphasal or naphazolin or Naphcon or "naphozoline hydrochloride" or naphtears or naphthazoline or naphthizine or naphthyzin or nastizol or "nazil ofteno" or niazol or "ocu‐zoline" or opcon or Optazine or Privin or privina or Privine or privine or Proculin or rhinantin or rhinazin or rhinoperd or rimidol or sanorin or sanotin or Siozwo or strictylon or "Tele Stulln" or TeleStulln or Vasoclear or Vasocon or "Vasoconstrictor Pensa" or VasoNit or vistalbalon or vistobalon or "5144‐52‐5" or "550‐99‐2" or "835‐31‐4" #33 Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5" #34 MeSH descriptor: [Synephrine] explode all trees #35 MeSH descriptor: [Oxyphenonium] explode all trees #36 Oxyphenonium or Methacin or Oxyphenon or Atrenyl or Spastrex or antrenyl or "ba 5473" or ba5473 or "c 5473" or c5473 or helkamon or metacin or metacinum or oxyphenium or "oxyphenomium bromide" or spasmofen or spasmophen or "14214‐84‐7" or "50‐10‐2" #37 MeSH descriptor: [Phenylephrine] explode all trees #38 Phenylephrine or adrianol or "af‐taf" or "ak‐dilate" or "albalon relief" or alconefrin or almefrin or altafrin or biomidrin or biomydrin or derizene or "despec‐sf" or "disneumon pernasal" or drosin or "efrin‐10" or efrisel or fenylephrine or idrianol or isonefrine or isophrin or isophrine or "isopto frin" or isoptofrin or lexatol or "m synephrine" or mesaton or "meta sympathol" or "meta synephrine" or Metaoxedrin or metaoxedrine or Metasympatol or metasynephrine or Mezaton or "murucoll 2" or mydfrin or "n 105 to" or "nefrin‐ofteno" or "Neo Synephrine" or neofrin or neooxedrine or neophryn or neosynephrin or Neosynephrine or "neosynephrin‐pos" or neosynesin or neosynesine or "ocu‐phrin" or "oftan‐metaoksedrin" or optistin or phenoptic or phenylefrine or phenylephedrine or prefrin or "pupiletto forte" or rectasol or "rhinall 10" or "slv 325" or slv325 or sucraphen or vazculep or visadron or vistafrin or vistosan or "532‐38‐7" or "59‐42‐7" or "61‐76‐7" #39 Pholedrine or "4 hydroxy n methylamphetamine" or "4 hydroxymethamphetamine" or adyston or "para hydroxymethamphetamine" or "p‐hydroxymethamphetamine" or paredrinol or "Pholedrin liquidum" or "Pholedrin‐longo‐Isis" or pulsotyl or venosan or veritol or "370‐14‐9" #40 MeSH descriptor: [p‐Hydroxyamphetamine] explode all trees #41 p‐Hydroxyamphetamine or "1 para hydroxyphenyl 2 propylamine" or "alpha methyl para tyramine" or "alpha methyl tyramine" or "dl 1 p hydroxyphenyl 2 propylamine" or "dl 1 para hydroxyphenyl 2 propylamine" or "dl p hydroxy alpha methylphenethylamine" or "dl para hydroxy alpha methylphenethylamine" or "h 66 37" or "para hydroxy alpha methylphenethylamine" or Hydroxyamfetamine or Hydroxyamphetamin or Hydroxyamphetamine or Hydroxyphenylisopropylamine or Methyltyramine or Norpholedrin or norpholedrine or oxamphetamine or Oxyamphetamine or paradrine or parahydroxyamphetamine or Paredrine or paredrinea or paredrinex or pedrolone or pulsoton or "103‐86‐6" or "1518‐86‐1" or "306‐21‐8" #42 MeSH descriptor: [Racepinephrine] explode all trees #43 Racepinephrine or asthmanefrin or Micronefrin or micronefrine or Micronephrine or mikronephrin or racadrenalin or "Racepinefrine Hydrochloride" or racinephrine or Vaponefrin or vaponefrine or vaponephrin or "329‐65‐7" #44 MeSH descriptor: [Scopolamine Hydrobromide] explode all trees #45 Scopolamine or "Boro Scopol" or BoroScopol or Hyoscine or Kwells or "levo hyoscinehydrobromide" or Scoburen or Scopace or scopos or "Travacalm HO" or Vorigeno or "114‐49‐8" or atrochin or atroquin or atroscine or hyosceine or hysco or "kimite‐patch" or "l epoxytropine tropate" or "n methylhyoscine" or oscine or scopalamine or "scopine tropate" or scopoderm or scopolamin or transcop or "transderm scop" or "transderm v" or "tropic acid ester with scopine" or "138‐12‐5" or "51‐34‐3" or "55‐16‐3" #46 MeSH descriptor: [Tropicamide] explode all trees #47 Tropicamide or "alcon‐mydril" or bistropamide or "cendo mydriatyl" or "Colircusi Tropicamida" or midriaticum or mydiacyl or mydral or mydramide or mydriacyl or Mydriafair or Mydriaticum or "mydrin m" or "mydrin p" or Mydrum or "n ethyl 2 phenyl n pyrid 4 ylmethylhydracrylamide" or "n ethyl n 4 picolyltropamide" or "n ethyl n gamma picolyltropamide" or "n ethyl n pyrid 4 ylmethyltropamide" or "Ocu‐Tropic" or OcuTropic or opticyl or sandol or sintropic or "tropamid forte" or "tropic acid n ethyl n gamma picolyl amide" or Tropicacyl or tropicamid or "tropico eye" or tropicol or tropikamid or tropimil or visumidriatic or "1508‐75‐4" #48 MeSH descriptor: [Tyramine] explode all trees #49 Tyramine or "4 hydroxyphenethylamine" or lyramine or mydrial or "para hydroxyphenethylamine" or paratyramine or systogene or tiramine or tocosine or tyramin or tyrosamine or uteramine or "51‐67‐2" or "60‐19‐5" #50 Vibrocil or "8059‐14‐1" #51 MeSH descriptor: [Yohimbine] explode all trees #52 Yohimbine or actibine or aphrodine or aphrodyne or Corynanthine or "corynine hydrochloride" or "dayto‐himbin" or "methyl yohimbine 16alpha carboxylate" or "methylyohimbane 16alpha carboxylate" or Pluriviron or quebrachin or "quebrachine hydrochloride" or Rauhimbine or Rauwolscine or urobine or yobin or yobinol or yocan or yocaral or Yocon or yocon or yohimbe or "yohimbic acid methyl ester" or yohimbin or Yohimex or yohimex or yohimibin or yovital or "146‐48‐5" or "65‐19‐0" #53 {or #9‐#52} #54 #8 and #53

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 Cataract/ 13. exp cataract extraction/ 14. (Cataract* adj4 (extract* or aspirat* or operat* or remov* or surg* or excis* or implant*)).tw. 15. (lens* adj4 (extract* or aspirat* or operat* or remov* or surg* or excis* or implant* or emulsif*)).tw. 16. (phakectom* or lensectom* or zonulolys* or catarectom*).tw. 17. (pha*oemulsif* or pha*o emulsif* or facoemulsif* or faco emulsif*).tw. 18. (Capsulorhexis or Capsulorrhexis).tw. 19. or/12‐18 20. exp Mydriasis/ 21. exp Miotics/ 22. exp Miosis/ 23. (Miotic* or Miosis or myosis or mydriasis or Mydriasert or (pupil* adj3 dilat*)).tw. 24. exp Mydriatics/ 25. mydriatic*.tw. 26. cycloplegic*.tw. 27. exp Atropine/ 28. (Atropine or atrinal or "atro‐polygyl" or atrop or atropen or atropin or atropina or "atropini sulfas" or atropinol or atropisol or atropt or atroptol or atrospan or "atrosulf‐1" or "bar bropin" or "bellpino‐artin" or "cendo tropine" or "dextro levo hyosciamine" or "ichtho bellol" or "isopto" or isoptoAtropine or "ocu‐tropine" or "sal‐tropine" or skiatropine or "tropine dextro levo tropate" or ximex or "51‐55‐8" or "55‐48‐1").tw. 29. ("51‐55‐8" or "55‐48‐1").rn. 30. (berefrine or POPD or "105567‐83‐7").tw. 31. "105567‐83‐7".rn. 32. exp Cyclopentolate/ 33. (Cyclopentolate or "ak‐pentolate" or akpentolate or "bell pentolate" or ciclolux or cyclogyl or cyclomydri or cyclopentol or cyclopentolat or cylate or cyplegin or diopentolate or midriodavi or mydrilate or "ocu‐pentolate" or ocucyclo or "oftan‐syklo" or pentolair or "refractyl ofeno" or skiacol or zyklolat or "512‐15‐2" or "5870‐29‐1").tw. 34. ("512‐15‐2" or "5870‐29‐1").rn. 35. exp Epinephrine/ 36. (Epinephrine or Adrenaline or adrenalin or Epitrate or Lyophrin or Epifrin or adnephrin or adnephrine or adrenaclick or "adrenal hydrochloride" or adrenalina or adrenamine or adrenapax or adrenazin or adrenine or adrin or adrine or advaradin or balmadren or biorenine or bosmin or chelafrin or dylephrin or epiglaufrin or epimephrine or epinefrina or epinephran or epinephrin or epirenamine or epirenan or exadrin or glaucon or glaucosan or glaufrin or "glin epin" or glycirenan or haemostatin or hemisine or hemostasin or hemostatin or hypernephrin or "isopto epinal" or levoadrenalin or levoadrenaline or levoepinephrine or levorenin or levorenine or methylaminoethanolcatechol or methylarterenol or mucidrina or myosthenine or "n methylnoradrenalin" or nephridine or nieraline or paranephrin or posumin or renaglandin or renaglandulin or renaleptine or renalina or renaline or renoform or renostypticin or renostyptin or scurenaline or simplene or soladren or sphygmogenin or styptirenal or supracapsulin or supranephrane or supranephrin or supranol or suprarenaline or suprarenin or suprarenine or suprel or surenine or surrenine or "sus‐phrine sulfite‐free" or susphrine or "sympathin I" or takamina or tonogen or vasoconstrictine or vasodrine or vasotonin or weradren or "51‐43‐4" or "55‐31‐2" or "6912‐68‐1").tw. 37. ("51‐43‐4" or "55‐31‐2" or "6912‐68‐1").rn. 38. exp Ethylmorphine/ 39. (Ethylmorphine or Ethomorphine or Trachyl or codethyline or diolan or dionine or "ethyl morphine" or ethylmorfine or ethylmorphin or "morphine ethyl ether" or "125‐30‐4" or "76‐58‐4").tw. 40. ("125‐30‐4" or "76‐58‐4").rn. 41. (Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6").tw. 42. ("100‐91‐4" or "536‐93‐6").rn. 43. (Homatropine or homatro or homatrocil or homatropaire or homatropin or homatropina or isoptoHomatropine or "I Homatrine" or "mandelyl tropeine" or mandelyltropeine or "mydryn eye" or "omatropina lux" or "tropine mandelate" or "51‐56‐9" or "87‐00‐3").tw. 44. ("51‐56‐9" or "87‐00‐3").rn. 45. exp Hyoscyamine/ 46. (Hyoscyamine or anaspaz or cystospaz or cytospaz or daturine or donnamar or duboisine or egacen or hyoscamine or hyosciamine or hyoscyanin or hyosyne or "ib‐stat" or levbid or levsin or "levsinex sr" or neosol or nulev or spasdel or "symax sl" or "symax sr" or "tropine l tropate" or "101‐31‐5" or "306‐03‐6").tw. 47. ("101‐31‐5" or "306‐03‐6").rn. 48. (Ibopamine or "N‐methyldopamine diisobutyrate" or "SB 7505" or "SB7505" or Escandine or Inopamil or "diisobutyric n methyldopamine ester" or scandine or "skf 100168" or "skf 100168 a" or "66195‐31‐1" or "75011‐65‐3").tw. 49. ("66195‐31‐1" or "75011‐65‐3").rn. 50. (Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4").tw. 51. "31610‐87‐4".rn. 52. exp Naphazoline/ 53. (Naphazoline or "Afazol Grin" or "AK Con" or AKCon or Albalon or albasol or "All Clear" or allersol or antan or benil or cefasan or "Clear Eyes" or coldan or "Colirio Alfa" or "comfort eye drops" or dazolin or "degest 2" or derinox or Idril or imidin or minha or Miraclar or mirafrin or Nafazair or nafazoline or naftazolina or "naphacel ofteno" or naphasal or naphazolin or Naphcon or "naphozoline hydrochloride" or naphtears or naphthazoline or naphthizine or naphthyzin or nastizol or "nazil ofteno" or niazol or "ocu‐zoline" or opcon or Optazine or Privin or privina or Privine or privine or Proculin or rhinantin or rhinazin or rhinoperd or rimidol or sanorin or sanotin or Siozwo or strictylon or "Tele Stulln" or TeleStulln or Vasoclear or Vasocon or "Vasoconstrictor Pensa" or VasoNit or vistalbalon or vistobalon or "5144‐52‐5" or "550‐99‐2" or "835‐31‐4").tw. 54. ("5144‐52‐5" or "550‐99‐2" or "835‐31‐4").rn. 55. (Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5").tw. 56. "94‐07‐5".rn. 57. exp Synephrine/ 58. exp Oxyphenonium/ 59. (Oxyphenonium or Methacin or Oxyphenon or Atrenyl or Spastrex or antrenyl or "ba 5473" or ba5473 or "c 5473" or c5473 or helkamon or metacin or metacinum or oxyphenium or "oxyphenomium bromide" or spasmofen or spasmophen or "14214‐84‐7" or "50‐10‐2").tw. 60. ("14214‐84‐7" or "50‐10‐2").rn. 61. exp Phenylephrine/ 62. (Phenylephrine or adrianol or "af‐taf" or "ak‐dilate" or "albalon relief" or alconefrin or almefrin or altafrin or biomidrin or biomydrin or derizene or "despec‐sf" or "disneumon pernasal" or drosin or "efrin‐10" or efrisel or fenylephrine or idrianol or isonefrine or isophrin or isophrine or "isopto frin" or isoptofrin or lexatol or "m synephrine" or mesaton or "meta sympathol" or "meta synephrine" or Metaoxedrin or metaoxedrine or Metasympatol or metasynephrine or Mezaton or "murucoll 2" or mydfrin or "n 105 to" or "nefrin‐ofteno" or "Neo Synephrine" or neofrin or neooxedrine or neophryn or neosynephrin or Neosynephrine or "neosynephrin‐pos" or neosynesin or neosynesine or "ocu‐phrin" or "oftan‐metaoksedrin" or optistin or phenoptic or phenylefrine or phenylephedrine or prefrin or "pupiletto forte" or rectasol or "rhinall 10" or "slv 325" or slv325 or sucraphen or vazculep or visadron or vistafrin or vistosan or "532‐38‐7" or "59‐42‐7" or "61‐76‐7").tw. 63. ("532‐38‐7" or "59‐42‐7" or "61‐76‐7").rn. 64. (Pholedrine or "4 hydroxy n methylamphetamine" or "4 hydroxymethamphetamine" or adyston or "para hydroxymethamphetamine" or "p‐hydroxymethamphetamine" or paredrinol or "Pholedrin liquidum" or "Pholedrin‐longo‐Isis" or pulsotyl or venosan or veritol or "370‐14‐9").tw. 65. "370‐14‐9".rn. 66. exp p‐Hydroxyamphetamine/ 67. (p‐Hydroxyamphetamine or "1 para hydroxyphenyl 2 propylamine" or "alpha methyl para tyramine" or "alpha methyl tyramine" or "dl 1 p hydroxyphenyl 2 propylamine" or "dl 1 para hydroxyphenyl 2 propylamine" or "dl p hydroxy alpha methylphenethylamine" or "dl para hydroxy alpha methylphenethylamine" or "h 66 37" or "para hydroxy alpha methylphenethylamine" or Hydroxyamfetamine or Hydroxyamphetamin or Hydroxyamphetamine or Hydroxyphenylisopropylamine or Methyltyramine or Norpholedrin or norpholedrine or oxamphetamine or Oxyamphetamine or paradrine or parahydroxyamphetamine or Paredrine or paredrinea or paredrinex or pedrolone or pulsoton or "103‐86‐6" or "1518‐86‐1" or "306‐21‐8").tw. 68. ("103‐86‐6" or "1518‐86‐1" or "306‐21‐8").rn. 69. exp Racepinephrine/ 70. (Racepinephrine or asthmanefrin or Micronefrin or micronefrine or Micronephrine or mikronephrin or racadrenalin or "Racepinefrine Hydrochloride" or racinephrine or Vaponefrin or vaponefrine or vaponephrin or "329‐65‐7").tw. 71. "329‐65‐7".rn. 72. exp Scopolamine Hydrobromide/ 73. (Scopolamine or "Boro Scopol" or BoroScopol or Hyoscine or Kwells or "levo hyoscinehydrobromide" or Scoburen or Scopace or scopos or "Travacalm HO" or Vorigeno or "114‐49‐8" or atrochin or atroquin or atroscine or hyosceine or hysco or "kimite‐patch" or "l epoxytropine tropate" or "n methylhyoscine" or oscine or scopalamine or "scopine tropate" or scopoderm or scopolamin or transcop or "transderm scop" or "transderm v" or "tropic acid ester with scopine" or "138‐12‐5" or "51‐34‐3" or "55‐16‐3").tw. 74. ("114‐49‐8" or "138‐12‐5" or "51‐34‐3" or "55‐16‐3").rn. 75. exp Tropicamide/ 76. (Tropicamide or "alcon‐mydril" or bistropamide or "cendo mydriatyl" or "Colircusi Tropicamida" or midriaticum or mydiacyl or mydral or mydramide or mydriacyl or Mydriafair or Mydriaticum or "mydrin m" or "mydrin p" or Mydrum or "n ethyl 2 phenyl n pyrid 4 ylmethylhydracrylamide" or "n ethyl n 4 picolyltropamide" or "n ethyl n gamma picolyltropamide" or "n ethyl n pyrid 4 ylmethyltropamide" or "Ocu‐Tropic" or OcuTropic or opticyl or sandol or sintropic or "tropamid forte" or "tropic acid n ethyl n gamma picolyl amide" or Tropicacyl or tropicamid or "tropico eye" or tropicol or tropikamid or tropimil or visumidriatic or "1508‐75‐4").tw. 77. "1508‐75‐4".rn. 78. exp Tyramine/ 79. (Tyramine or "4 hydroxyphenethylamine" or lyramine or mydrial or "para hydroxyphenethylamine" or paratyramine or systogene or tiramine or tocosine or tyramin or tyrosamine or uteramine or "51‐67‐2" or "60‐19‐5").tw. 80. ("51‐67‐2" or "60‐19‐5").rn. 81. (Vibrocil or "8059‐14‐1").tw. 82. "8059‐14‐1".rn. 83. exp Yohimbine/ 84. (Yohimbine or actibine or aphrodine or aphrodyne or Corynanthine or "corynine hydrochloride" or "dayto‐himbin" or "methyl yohimbine 16alpha carboxylate" or "methylyohimbane 16alpha carboxylate" or Pluriviron or quebrachin or "quebrachine hydrochloride" or Rauhimbine or Rauwolscine or urobine or yobin or yobinol or yocan or yocaral or Yocon or yocon or yohimbe or "yohimbic acid methyl ester" or yohimbin or Yohimex or yohimex or yohimibin or yovital or "146‐48‐5" or "65‐19‐0").tw. 85. ("146‐48‐5" or "65‐19‐0").rn. 86. or/20‐85 87. 19 and 86 88. 11 and 87

The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by 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 'cataract'/exp #34 'cataract extraction'/exp #35 ((extract* OR aspirat* OR operat* OR remov* OR surg* OR excis* OR implant*) NEAR/4 (cataract*)):ab,ti #36 ((extract* OR aspirat* OR operat* OR remov* OR surg* OR excis* OR implant* OR emulsif*) NEAR/4 (lens*)):ab,ti #37 (phakectom* OR lensectom* OR zonulolys* OR catarectom*):ab,ti #38 (pha*oemulsif* OR ("pha*o emulsif*") OR facoemulsif* OR ("faco emulsif*")):ab,ti #39 (Capsulorhexis OR Capsulorrhexis):ab,ti #40 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 #41 'mydriasis'/exp #42 'miotic agent'/exp #43 'miosis'/exp #44 (Miotic* OR Miosis OR myosis OR mydriasis OR Mydriasert OR (pupil* NEAR/3 dilat*)):ab,ti #45 'mydriatic agent'/exp #46 mydriatic*:ti,ab #47 cycloplegic*:ti,ab #48 (Atropine OR atrinal OR "atro‐polygyl" OR atrop OR atropen OR atropin OR atropina OR "atropini sulfas" OR atropinol OR atropisol OR atropt OR atroptol OR atrospan OR "atrosulf‐1" OR "bar bropin" OR "bellpino‐artin" OR "cendo tropine" OR "dextro levo hyosciamine" OR "ichtho bellol" OR "isopto" OR isoptoAtropine OR "ocu‐tropine" OR "sal‐tropine" OR skiatropine OR "tropine dextro levo tropate" OR ximex OR "51‐55‐8" OR "55‐48‐1"):ab,ti,tn #49 (berefrine OR POPD OR "105567‐83‐7"):ab,ti,tn #50 (Cyclopentolate OR "ak‐pentolate" OR akpentolate OR "bell pentolate" OR ciclolux OR cyclogyl OR cyclomydri OR cyclopentol OR cyclopentolat OR cylate OR cyplegin OR diopentolate OR midriodavi OR mydrilate OR "ocu‐pentolate" OR ocucyclo OR "oftan‐syklo" OR pentolair OR "refractyl ofeno" OR skiacol OR zyklolat OR "512‐15‐2" OR "5870‐29‐1"):ab,ti,tn #51 'adrenalin'/exp #52 (Epinephrine OR Adrenaline OR adrenalin OR Epitrate OR Lyophrin OR Epifrin OR adnephrin OR adnephrine OR "adrenal hydrochloride" OR adrenalina OR adrenamine OR adrenapax OR adrenazin OR adrenine OR adrin OR adrine OR advaradin OR balmadren OR biorenine OR bosmin OR chelafrin OR dylephrin OR epiglaufrin OR epimephrine OR epinefrina OR epinephran OR epinephrin OR epirenamine OR epirenan OR exadrin OR glaucon OR glaucosan OR glaufrin OR "glin epin" OR glycirenan OR haemostatin OR hemisine OR hemostasin OR hemostatin OR hypernephrin OR "isopto epinal" OR levoadrenalin OR levoadrenaline OR levoepinephrine OR levorenin OR levorenine OR methylaminoethanolcatechol OR methylarterenol OR mucidrina OR myosthenine OR "n methylnoradrenalin" OR nephridine OR nieraline OR paranephrin OR posumin OR renaglandin OR renaglandulin OR renaleptine OR renalina OR renaline OR renoform OR renostypticin OR renostyptin OR scurenaline OR simplene OR soladren OR sphygmogenin OR styptirenal OR supracapsulin OR supranephrane OR supranephrin OR supranol OR suprarenaline OR suprarenin OR suprarenine OR suprel OR surenine OR surrenine OR "sus‐phrine sulfite‐free" OR susphrine OR "sympathin I" OR takamina OR tonogen OR vasoconstrictine OR vasodrine OR vasotonin OR weradren OR "51‐43‐4" OR "55‐31‐2" OR "6912‐68‐1"):ab,ti,tn #53 (Ethylmorphine OR Ethomorphine OR Trachyl OR codethyline OR diolan OR dionine OR "ethyl morphine" OR ethylmorfine OR ethylmorphin OR "morphine ethyl ether" OR "125‐30‐4" OR "76‐58‐4"):ab,ti,tn #54 (Eucatropine OR euphthalmine OR "100‐91‐4" OR "536‐93‐6"):ab,ti,tn #55 (Homatropine OR homatro OR homatrocil OR homatropaire OR homatropin OR homatropina OR isoptoHomatropine OR "I Homatrine" OR "mandelyl tropeine" OR mandelyltropeine OR "mydryn eye" OR "omatropina lux" OR "tropine mandelate" OR "51‐56‐9" OR "87‐00‐3"):ab,ti,tn #56 'hyoscyamine'/exp #57 (Hyoscyamine OR anaspaz OR cystospaz OR cytospaz OR daturine OR donnamar OR duboisine OR egacen OR hyoscamine OR hyosciamine OR hyoscyanin OR hyosyne OR "ib‐stat" OR levbid OR levsin OR "levsinex sr" OR neosol OR nulev OR spasdel OR "symax sl" OR "symax sr" OR "tropine l tropate" OR "101‐31‐5" OR "306‐03‐6"):ab,ti,tn #58 'ibopamine'/exp #59 (Ibopamine OR "N‐methyldopamine diisobutyrate" OR "SB 7505" OR "SB7505" OR Escandine OR Inopamil OR "diisobutyric n methyldopamine ester" OR scandine OR "skf 100168" OR "skf 100168 a" OR "66195‐31‐1" OR "75011‐65‐3"):ti,ab,tn #60 (Methylatropine OR "8‐methylatropinium nitrate" OR "31610‐87‐4"):ti,ab,tn #61 (Naphazoline OR "Afazol Grin" OR "AK Con" OR AKCon OR Albalon OR albasol OR "All Clear" OR allersol OR antan OR benil OR cefasan OR "Clear Eyes" OR coldan OR "Colirio Alfa" OR "comfort eye drops" OR dazolin OR "degest 2" OR derinox OR Idril OR imidin OR minha OR Miraclar OR mirafrin OR Nafazair OR nafazoline OR naftazolina OR "naphacel ofteno" OR naphasal OR naphazolin OR Naphcon OR "naphozoline hydrochloride" OR naphtears OR naphthazoline OR naphthizine OR naphthyzin OR nastizol OR "nazil ofteno" OR niazol OR "ocu‐zoline" OR opcon OR Optazine OR Privin OR privina OR Privine OR privine OR Proculin OR rhinantin OR rhinazin OR rhinoperd OR rimidol OR sanorin OR sanotin OR Siozwo OR strictylon OR "Tele Stulln" OR TeleStulln OR Vasoclear OR Vasocon OR "Vasoconstrictor Pensa" OR VasoNit OR vistalbalon OR vistobalon OR "5144‐52‐5" OR "550‐99‐2" OR "835‐31‐4"):ti,ab,tn #62 (Oxedrine OR Synephrine OR Sympaethamin OR Synephrin OR aetaphen OR pentedrine OR vasoton OR "94‐07‐5"):ti,ab,tn #63 'oxyphenonium bromide'/exp #64 (Oxyphenonium OR Methacin OR Oxyphenon OR Atrenyl OR Spastrex OR antrenyl OR "ba 5473" OR ba5473 OR "c 5473" OR c5473 OR helkamon OR metacin OR metacinum OR oxyphenium OR "oxyphenomium bromide" OR spasmofen OR spasmophen OR "14214‐84‐7" OR "50‐10‐2"):ab,ti,tn #65 (Phenylephrine OR adrianol OR "af‐taf" OR "ak‐dilate" OR "albalon relief" OR alconefrin OR almefrin OR altafrin OR biomidrin OR biomydrin OR derizene OR "despec‐sf" OR drosin OR "efrin‐10" OR efrisel OR fenylephrine OR idrianol OR isonefrine OR isophrin OR isophrine OR "isopto frin" OR isoptofrin OR lexatol OR "m synephrine" OR mesaton OR "meta sympathol" OR "meta synephrine" OR Metaoxedrin OR metaoxedrine OR Metasympatol OR metasynephrine OR Mezaton OR "murucoll 2" OR mydfrin OR "n 105 to" OR "nefrin‐ofteno" OR "Neo Synephrine" OR neofrin OR neooxedrine OR neophryn OR neosynephrin OR Neosynephrine OR "neosynephrin‐pos" OR neosynesin OR neosynesine OR "ocu‐phrin" OR "oftan‐metaoksedrin" OR optistin OR phenoptic OR phenylefrine OR phenylephedrine OR prefrin OR "pupiletto forte" OR rectasol OR "rhinall 10" OR "slv 325" OR slv325 OR sucraphen OR vazculep OR visadron OR vistafrin OR vistosan OR "532‐38‐7" OR "59‐42‐7" OR "61‐76‐7"):ti,ab,tn #66 (Pholedrine OR "4 hydroxy n methylamphetamine" OR "4 hydroxymethamphetamine" OR adyston OR "para hydroxymethamphetamine" OR "p‐hydroxymethamphetamine" OR paredrinol OR "Pholedrin liquidum" OR "Pholedrin‐longo‐Isis" OR pulsotyl OR venosan OR veritol OR "370‐14‐9"):ti,ab,tn #67 'hydroxyamphetamine'/exp #68 (p‐Hydroxyamphetamine OR "1 para hydroxyphenyl 2 propylamine" OR "alpha methyl para tyramine" OR "alpha methyl tyramine" OR "dl 1 p hydroxyphenyl 2 propylamine" OR "dl 1 para hydroxyphenyl 2 propylamine" OR "dl p hydroxy alpha methylphenethylamine" OR "dl para hydroxy alpha methylphenethylamine" OR "h 66 37" OR "para hydroxy alpha methylphenethylamine" OR Hydroxyamfetamine OR Hydroxyamphetamin OR Hydroxyamphetamine OR Hydroxyphenylisopropylamine OR Methyltyramine OR Norpholedrin OR norpholedrine OR oxamphetamine OR Oxyamphetamine OR paradrine OR parahydroxyamphetamine OR Paredrine OR paredrinea OR paredrinex OR pedrolone OR pulsoton OR "103‐86‐6" OR "1518‐86‐1" OR "306‐21‐8"):ab,ti,tn #69 'racepinefrine'/exp #70 (Racepinephrine OR Micronefrin OR micronefrine OR Micronephrine OR mikronephrin OR racadrenalin OR "Racepinefrine Hydrochloride" OR racinephrine OR Vaponefrin OR vaponefrine OR vaponephrin OR "329‐65‐7"):ti,ab,tn #71 'scopolamine bromide'/exp #72 (Scopolamine OR "Boro Scopol" OR BoroScopol OR Hyoscine OR Kwells OR "levo hyoscinehydrobromide" OR Scoburen OR Scopace OR scopos OR "Travacalm HO" OR Vorigeno OR "114‐49‐8" OR atrochin OR atroquin OR atroscine OR hyosceine OR hysco OR "l epoxytropine tropate" OR "n methylhyoscine" OR oscine OR scopalamine OR "scopine tropate" OR scopolamin OR transcop OR "tropic acid ester with scopine" OR "138‐12‐5" OR "51‐34‐3" OR "55‐16‐3"):ab,ti,tn #73 (Tropicamide OR "alcon‐mydril" OR bistropamide OR "cendo mydriatyl" OR "Colircusi Tropicamida" OR midriaticum OR mydiacyl OR mydral OR mydramide OR mydriacyl OR Mydriafair OR Mydriaticum OR "mydrin m" OR "mydrin p" OR Mydrum OR "n ethyl 2 phenyl n pyrid 4 ylmethylhydracrylamide" OR "n ethyl n 4 picolyltropamide" OR "n ethyl n gamma picolyltropamide" OR "n ethyl n pyrid 4 ylmethyltropamide" OR "Ocu‐Tropic" OR OcuTropic OR opticyl OR sandol OR sintropic OR "tropamid forte" OR "tropic acid n ethyl n gamma picolyl amide" OR Tropicacyl OR tropicamid OR "tropico eye" OR tropicol OR tropikamid OR tropimil OR visumidriatic OR "1508‐75‐4"):ab,ti,tn #74 (Tyramine OR "4 hydroxyphenethylamine" OR lyramine OR mydrial OR "para hydroxyphenethylamine" OR paratyramine OR systogene OR tiramine OR tocosine OR tyramin OR tyrosamine OR uteramine OR "51‐67‐2" OR "60‐19‐5"):ti,ab,tn #75 (Vibrocil OR "8059‐14‐1"):ti,ab,tn #76 'yohimbine'/exp #77 (Yohimbine OR actibine OR aphrodine OR aphrodyne OR Corynanthine OR "corynine hydrochloride" OR "dayto‐himbin" OR "methyl yohimbine 16alpha carboxylate" OR "methylyohimbane 16alpha carboxylate" OR Pluriviron OR quebrachin OR "quebrachine hydrochloride" OR Rauhimbine OR Rauwolscine OR urobine OR yobin OR yobinol OR yocan OR yocaral OR Yocon OR yocon OR yohimbe OR "yohimbic acid methyl ester" OR yohimbin OR Yohimex OR yohimex OR yohimibin OR yovital OR "146‐48‐5" OR "65‐19‐0"):ti,ab,tn #78 #41 OR #42 OR #43 OR #44 OR #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 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76 OR #77 #79 #40 AND #78 #80 #32 AND #79

Appendix 4. PubMed 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 'cataract'/exp #34 'cataract extraction'/exp #35 ((extract* OR aspirat* OR operat* OR remov* OR surg* OR excis* OR implant*) NEAR/4 (cataract*)):ab,ti #36 ((extract* OR aspirat* OR operat* OR remov* OR surg* OR excis* OR implant* OR emulsif*) NEAR/4 (lens*)):ab,ti #37 (phakectom* OR lensectom* OR zonulolys* OR catarectom*):ab,ti #38 (pha*oemulsif* OR ("pha*o emulsif*") OR facoemulsif* OR ("faco emulsif*")):ab,ti #39 (Capsulorhexis OR Capsulorrhexis):ab,ti #40 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 #41 'mydriasis'/exp #42 'miotic agent'/exp #43 'miosis'/exp #44 (Miotic* OR Miosis OR myosis OR mydriasis OR Mydriasert OR (pupil* NEAR/3 dilat*)):ab,ti #45 'mydriatic agent'/exp #46 mydriatic*:ti,ab #47 cycloplegic*:ti,ab #48 (Atropine OR atrinal OR "atro‐polygyl" OR atrop OR atropen OR atropin OR atropina OR "atropini sulfas" OR atropinol OR atropisol OR atropt OR atroptol OR atrospan OR "atrosulf‐1" OR "bar bropin" OR "bellpino‐artin" OR "cendo tropine" OR "dextro levo hyosciamine" OR "ichtho bellol" OR "isopto" OR isoptoAtropine OR "ocu‐tropine" OR "sal‐tropine" OR skiatropine OR "tropine dextro levo tropate" OR ximex OR "51‐55‐8" OR "55‐48‐1"):ab,ti,tn #49 (berefrine OR POPD OR "105567‐83‐7"):ab,ti,tn #50 (Cyclopentolate OR "ak‐pentolate" OR akpentolate OR "bell pentolate" OR ciclolux OR cyclogyl OR cyclomydri OR cyclopentol OR cyclopentolat OR cylate OR cyplegin OR diopentolate OR midriodavi OR mydrilate OR "ocu‐pentolate" OR ocucyclo OR "oftan‐syklo" OR pentolair OR "refractyl ofeno" OR skiacol OR zyklolat OR "512‐15‐2" OR "5870‐29‐1"):ab,ti,tn #51 'adrenalin'/exp #52 (Epinephrine OR Adrenaline OR adrenalin OR Epitrate OR Lyophrin OR Epifrin OR adnephrin OR adnephrine OR "adrenal hydrochloride" OR adrenalina OR adrenamine OR adrenapax OR adrenazin OR adrenine OR adrin OR adrine OR advaradin OR balmadren OR biorenine OR bosmin OR chelafrin OR dylephrin OR epiglaufrin OR epimephrine OR epinefrina OR epinephran OR epinephrin OR epirenamine OR epirenan OR exadrin OR glaucon OR glaucosan OR glaufrin OR "glin epin" OR glycirenan OR haemostatin OR hemisine OR hemostasin OR hemostatin OR hypernephrin OR "isopto epinal" OR levoadrenalin OR levoadrenaline OR levoepinephrine OR levorenin OR levorenine OR methylaminoethanolcatechol OR methylarterenol OR mucidrina OR myosthenine OR "n methylnoradrenalin" OR nephridine OR nieraline OR paranephrin OR posumin OR renaglandin OR renaglandulin OR renaleptine OR renalina OR renaline OR renoform OR renostypticin OR renostyptin OR scurenaline OR simplene OR soladren OR sphygmogenin OR styptirenal OR supracapsulin OR supranephrane OR supranephrin OR supranol OR suprarenaline OR suprarenin OR suprarenine OR suprel OR surenine OR surrenine OR "sus‐phrine sulfite‐free" OR susphrine OR "sympathin I" OR takamina OR tonogen OR vasoconstrictine OR vasodrine OR vasotonin OR weradren OR "51‐43‐4" OR "55‐31‐2" OR "6912‐68‐1"):ab,ti,tn #53 (Ethylmorphine OR Ethomorphine OR Trachyl OR codethyline OR diolan OR dionine OR "ethyl morphine" OR ethylmorfine OR ethylmorphin OR "morphine ethyl ether" OR "125‐30‐4" OR "76‐58‐4"):ab,ti,tn #54 (Eucatropine OR euphthalmine OR "100‐91‐4" OR "536‐93‐6"):ab,ti,tn #55 (Homatropine OR homatro OR homatrocil OR homatropaire OR homatropin OR homatropina OR isoptoHomatropine OR "I Homatrine" OR "mandelyl tropeine" OR mandelyltropeine OR "mydryn eye" OR "omatropina lux" OR "tropine mandelate" OR "51‐56‐9" OR "87‐00‐3"):ab,ti,tn #56 'hyoscyamine'/exp #57 (Hyoscyamine OR anaspaz OR cystospaz OR cytospaz OR daturine OR donnamar OR duboisine OR egacen OR hyoscamine OR hyosciamine OR hyoscyanin OR hyosyne OR "ib‐stat" OR levbid OR levsin OR "levsinex sr" OR neosol OR nulev OR spasdel OR "symax sl" OR "symax sr" OR "tropine l tropate" OR "101‐31‐5" OR "306‐03‐6"):ab,ti,tn #58 'ibopamine'/exp #59 (Ibopamine OR "N‐methyldopamine diisobutyrate" OR "SB 7505" OR "SB7505" OR Escandine OR Inopamil OR "diisobutyric n methyldopamine ester" OR scandine OR "skf 100168" OR "skf 100168 a" OR "66195‐31‐1" OR "75011‐65‐3"):ti,ab,tn #60 (Methylatropine OR "8‐methylatropinium nitrate" OR "31610‐87‐4"):ti,ab,tn #61 (Naphazoline OR "Afazol Grin" OR "AK Con" OR AKCon OR Albalon OR albasol OR "All Clear" OR allersol OR antan OR benil OR cefasan OR "Clear Eyes" OR coldan OR "Colirio Alfa" OR "comfort eye drops" OR dazolin OR "degest 2" OR derinox OR Idril OR imidin OR minha OR Miraclar OR mirafrin OR Nafazair OR nafazoline OR naftazolina OR "naphacel ofteno" OR naphasal OR naphazolin OR Naphcon OR "naphozoline hydrochloride" OR naphtears OR naphthazoline OR naphthizine OR naphthyzin OR nastizol OR "nazil ofteno" OR niazol OR "ocu‐zoline" OR opcon OR Optazine OR Privin OR privina OR Privine OR privine OR Proculin OR rhinantin OR rhinazin OR rhinoperd OR rimidol OR sanorin OR sanotin OR Siozwo OR strictylon OR "Tele Stulln" OR TeleStulln OR Vasoclear OR Vasocon OR "Vasoconstrictor Pensa" OR VasoNit OR vistalbalon OR vistobalon OR "5144‐52‐5" OR "550‐99‐2" OR "835‐31‐4"):ti,ab,tn #62 (Oxedrine OR Synephrine OR Sympaethamin OR Synephrin OR aetaphen OR pentedrine OR vasoton OR "94‐07‐5"):ti,ab,tn #63 'oxyphenonium bromide'/exp #64 (Oxyphenonium OR Methacin OR Oxyphenon OR Atrenyl OR Spastrex OR antrenyl OR "ba 5473" OR ba5473 OR "c 5473" OR c5473 OR helkamon OR metacin OR metacinum OR oxyphenium OR "oxyphenomium bromide" OR spasmofen OR spasmophen OR "14214‐84‐7" OR "50‐10‐2"):ab,ti,tn #65 (Phenylephrine OR adrianol OR "af‐taf" OR "ak‐dilate" OR "albalon relief" OR alconefrin OR almefrin OR altafrin OR biomidrin OR biomydrin OR derizene OR "despec‐sf" OR drosin OR "efrin‐10" OR efrisel OR fenylephrine OR idrianol OR isonefrine OR isophrin OR isophrine OR "isopto frin" OR isoptofrin OR lexatol OR "m synephrine" OR mesaton OR "meta sympathol" OR "meta synephrine" OR Metaoxedrin OR metaoxedrine OR Metasympatol OR metasynephrine OR Mezaton OR "murucoll 2" OR mydfrin OR "n 105 to" OR "nefrin‐ofteno" OR "Neo Synephrine" OR neofrin OR neooxedrine OR neophryn OR neosynephrin OR Neosynephrine OR "neosynephrin‐pos" OR neosynesin OR neosynesine OR "ocu‐phrin" OR "oftan‐metaoksedrin" OR optistin OR phenoptic OR phenylefrine OR phenylephedrine OR prefrin OR "pupiletto forte" OR rectasol OR "rhinall 10" OR "slv 325" OR slv325 OR sucraphen OR vazculep OR visadron OR vistafrin OR vistosan OR "532‐38‐7" OR "59‐42‐7" OR "61‐76‐7"):ti,ab,tn #66 (Pholedrine OR "4 hydroxy n methylamphetamine" OR "4 hydroxymethamphetamine" OR adyston OR "para hydroxymethamphetamine" OR "p‐hydroxymethamphetamine" OR paredrinol OR "Pholedrin liquidum" OR "Pholedrin‐longo‐Isis" OR pulsotyl OR venosan OR veritol OR "370‐14‐9"):ti,ab,tn #67 'hydroxyamphetamine'/exp #68 (p‐Hydroxyamphetamine OR "1 para hydroxyphenyl 2 propylamine" OR "alpha methyl para tyramine" OR "alpha methyl tyramine" OR "dl 1 p hydroxyphenyl 2 propylamine" OR "dl 1 para hydroxyphenyl 2 propylamine" OR "dl p hydroxy alpha methylphenethylamine" OR "dl para hydroxy alpha methylphenethylamine" OR "h 66 37" OR "para hydroxy alpha methylphenethylamine" OR Hydroxyamfetamine OR Hydroxyamphetamin OR Hydroxyamphetamine OR Hydroxyphenylisopropylamine OR Methyltyramine OR Norpholedrin OR norpholedrine OR oxamphetamine OR Oxyamphetamine OR paradrine OR parahydroxyamphetamine OR Paredrine OR paredrinea OR paredrinex OR pedrolone OR pulsoton OR "103‐86‐6" OR "1518‐86‐1" OR "306‐21‐8"):ab,ti,tn #69 'racepinefrine'/exp #70 (Racepinephrine OR Micronefrin OR micronefrine OR Micronephrine OR mikronephrin OR racadrenalin OR "Racepinefrine Hydrochloride" OR racinephrine OR Vaponefrin OR vaponefrine OR vaponephrin OR "329‐65‐7"):ti,ab,tn #71 'scopolamine bromide'/exp #72 (Scopolamine OR "Boro Scopol" OR BoroScopol OR Hyoscine OR Kwells OR "levo hyoscinehydrobromide" OR Scoburen OR Scopace OR scopos OR "Travacalm HO" OR Vorigeno OR "114‐49‐8" OR atrochin OR atroquin OR atroscine OR hyosceine OR hysco OR "l epoxytropine tropate" OR "n methylhyoscine" OR oscine OR scopalamine OR "scopine tropate" OR scopolamin OR transcop OR "tropic acid ester with scopine" OR "138‐12‐5" OR "51‐34‐3" OR "55‐16‐3"):ab,ti,tn #73 (Tropicamide OR "alcon‐mydril" OR bistropamide OR "cendo mydriatyl" OR "Colircusi Tropicamida" OR midriaticum OR mydiacyl OR mydral OR mydramide OR mydriacyl OR Mydriafair OR Mydriaticum OR "mydrin m" OR "mydrin p" OR Mydrum OR "n ethyl 2 phenyl n pyrid 4 ylmethylhydracrylamide" OR "n ethyl n 4 picolyltropamide" OR "n ethyl n gamma picolyltropamide" OR "n ethyl n pyrid 4 ylmethyltropamide" OR "Ocu‐Tropic" OR OcuTropic OR opticyl OR sandol OR sintropic OR "tropamid forte" OR "tropic acid n ethyl n gamma picolyl amide" OR Tropicacyl OR tropicamid OR "tropico eye" OR tropicol OR tropikamid OR tropimil OR visumidriatic OR "1508‐75‐4"):ab,ti,tn #74 (Tyramine OR "4 hydroxyphenethylamine" OR lyramine OR mydrial OR "para hydroxyphenethylamine" OR paratyramine OR systogene OR tiramine OR tocosine OR tyramin OR tyrosamine OR uteramine OR "51‐67‐2" OR "60‐19‐5"):ti,ab,tn #75 (Vibrocil OR "8059‐14‐1"):ti,ab,tn #76 'yohimbine'/exp #77 (Yohimbine OR actibine OR aphrodine OR aphrodyne OR Corynanthine OR "corynine hydrochloride" OR "dayto‐himbin" OR "methyl yohimbine 16alpha carboxylate" OR "methylyohimbane 16alpha carboxylate" OR Pluriviron OR quebrachin OR "quebrachine hydrochloride" OR Rauhimbine OR Rauwolscine OR urobine OR yobin OR yobinol OR yocan OR yocaral OR Yocon OR yocon OR yohimbe OR "yohimbic acid methyl ester" OR yohimbin OR Yohimex OR yohimex OR yohimibin OR yovital OR "146‐48‐5" OR "65‐19‐0"):ti,ab,tn #78 #41 OR #42 OR #43 OR #44 OR #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 OR #67 OR #68 OR #69 OR #70 OR #71 OR #72 OR #73 OR #74 OR #75 OR #76 OR #77 #79 #40 AND #78 #80 #32 AND #79

Appendix 5. LILACS search strategy

(MH:C11.510.245$ OR MH:E04.540.825.249$ OR MH:E04.943.875$ OR phacoemulsif$ OR phakoemulsif$ OR phaco$ OR phako$ OR capsulorhexis or capsulorrhexis OR phakectom$ OR lensectom$ OR zonulolys$ OR catarectom$ OR cataract$) AND (MH:C11.710.570$ OR MH:D27.505.696.663.050.495$ OR MH:C10.597.690.362$ OR MH:C11.710.528$ OR MH:C23.888.592.708.362$ OR MH:D27.505.696.663.050.500$ OR Miotic$ OR Miosis OR Miose OR myosis OR mydriasis OR Midrias$ OR Mydriasert OR (pupil$ AND dilat$) OR mydriatic$ OR Midriáticos OR cycloplegic$ OR Atropin$ OR MH:D02.145.074.722.229.199$ OR MH:D03.132.760.180.572.199$ OR MH:D03.132.889.180.648.199$ OR MH:D03.605.869.229.199$ OR MH:D04.075.080.875.099.722.229.199 OR berefrine OR Cyclopentolate OR Ciclopentolato OR MH:D02.241.223.601.200$ OR Epinephrine OR Epinefrina OR MH:D02.033.100.291.310$ OR MH:D02.092.063.291.310$ OR MH:D02.092.211.215.311.461$ OR MH:D02.092.311.461$ OR Ethylmorphine OR Etilmorfina OR MH:D03.132.577.249.562.430$ OR MH:D03.549.686.607.460$ OR MH:D03.605.497.607.460$ OR MH:D04.615.723.795.576.430$ OR Eucatropine OR Homatropine OR Hyoscyamine OR Hiosciamina OR MH:D02.145.074.722.229.199.500$ OR MH:D03.132.760.180.572.199.500$ OR MH:D03.132.889.180.648.199.500$ OR MH:D03.605.869.229.199.500$ OR MH:D04.075.080.875.099.722.229.199.500$ OR Ibopamine OR Methylatropine OR Naphazoline OR Nafazolina OR MH:D03.383.129.308.585$ OR Oxedrine OR Synephrine OR Sinefrina OR MH:D02.033.100.291.870$ OR MH:D02.092.063.291.870$ OR MH:D02.092.211.215.811.875$ OR Oxyphenonium OR Oxifenonio OR MH:D02.092.877.648$ OR MH:D02.675.276.648$ OR Phenylephrine OR Fenilefrina OR MH:D02.033.100.291.617$ OR MH:D02.092.063.291.617$ OR Pholedrine OR "p‐Hydroxyamphetamine" OR "p‐Hidroxianfetamina" OR MH:D02.092.471.683.152.500$ OR Racepinephrine OR Racepinefrina OR MH:D02.033.100.291.310.500$ OR MH:D02.092.063.291.310.500$ OR MH:D02.092.211.215.311.461.700$ OR MH:D02.092.311.461.825$ OR Scopolamine OR Escopolamina OR MH:D02.145.074.722.822.775$ OR MH:D03.132.760.180.848$ OR MH:D03.132.889.601.775$ OR MH:D03.605.869.822.775$ OR MH:D04.075.080.875.099.722.822.775$ OR Tropicamide OR Tropicamida OR MH:D03.383.725.942$ OR Tyramine OR Tiramina OR MH:D02.092.211.215.811$ OR Vibrocil OR Yohimbine OR Yohimbina OR Ioimbina OR MH:D03.132.436.681.933$ OR MH:D03.438.473.402.681.933$)

Appendix 6. ClinicalTrials.gov search strategy

(Cataract OR Phacoemulsification OR Capsulorhexis) AND (mydriatics OR miotics OR miosis OR myosis OR mydriasis OR atropine OR berefrine OR cyclopentolate OR epinephrine OR ethylmorphine OR eucatropine OR homatropine OR hyoscyamine OR ibopamine OR oxyphenonium) (Cataract OR Phacoemulsification OR Capsulorhexis) AND (methylatropine OR naphazoline OR oxedrine OR p‐hydroxyamphetamine OR phenylephrine OR pholedrine OR scopolamine OR tropicamide OR tyramine OR vibrocil OR yohimbine)

Appendix 7. WHO ICTRP search strategy

Cataract AND mydriatics OR Cataract AND miotics OR Cataract AND miosis OR Cataract AND myosis OR Cataract AND mydriasis OR Cataract AND atropine OR Cataract AND berefrine OR Cataract AND cyclopentolate OR Cataract AND epinephrine OR Cataract AND ethylmorphine OR Cataract AND eucatropine OR Cataract AND homatropine OR Cataract AND hyoscyamine OR Cataract AND ibopamine OR Cataract AND oxyphenonium OR Cataract AND methylatropine OR Cataract AND naphazoline OR Cataract AND oxedrine OR Cataract AND p‐hydroxyamphetamine OR Cataract AND phenylephrine OR Cataract AND pholedrine OR Cataract AND scopolamine OR Cataract AND tropicamide OR Cataract AND tyramine OR Cataract AND vibrocil OR Cataract AND yohimbine

Phacoemulsification AND mydriatics OR Phacoemulsification AND miotics OR Phacoemulsification AND miosis OR Phacoemulsification AND myosis OR Phacoemulsification AND mydriasis OR Phacoemulsification AND atropine OR Phacoemulsification AND berefrine OR Phacoemulsification AND cyclopentolate OR Phacoemulsification AND epinephrine OR Phacoemulsification AND ethylmorphine OR Phacoemulsification AND eucatropine OR Phacoemulsification AND homatropine OR Phacoemulsification AND hyoscyamine OR Phacoemulsification AND ibopamine OR Phacoemulsification AND oxyphenonium OR Phacoemulsification AND methylatropine OR Phacoemulsification AND naphazoline OR Phacoemulsification AND oxedrine OR Phacoemulsification AND p‐hydroxyamphetamine OR Phacoemulsification AND phenylephrine OR Phacoemulsification AND pholedrine OR Phacoemulsification AND scopolamine OR Phacoemulsification AND tropicamide OR Phacoemulsification AND tyramine OR Phacoemulsification AND vibrocil OR Phacoemulsification AND yohimbine

Capsulorhexis AND mydriatics OR Capsulorhexis AND miotics OR Capsulorhexis AND miosis OR Capsulorhexis AND myosis OR Capsulorhexis AND mydriasis OR Capsulorhexis AND atropine OR Capsulorhexis AND berefrine OR Capsulorhexis AND cyclopentolate OR Capsulorhexis AND epinephrine OR Capsulorhexis AND ethylmorphine OR Capsulorhexis AND eucatropine OR Capsulorhexis AND homatropine OR Capsulorhexis AND hyoscyamine OR Capsulorhexis AND ibopamine OR Capsulorhexis AND oxyphenonium OR Capsulorhexis AND methylatropine OR Capsulorhexis AND naphazoline OR Capsulorhexis AND oxedrine OR Capsulorhexis AND p‐hydroxyamphetamine OR Capsulorhexis AND phenylephrine OR Capsulorhexis AND pholedrine OR Capsulorhexis AND scopolamine OR Capsulorhexis AND tropicamide OR Capsulorhexis AND tyramine OR Capsulorhexis AND vibrocil OR Capsulorhexis AND yohimbine

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 eye 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 reported only for the people who were followed up, 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

• Conception and design of study: Fasika A Woreta, Tahreem A Mir, Henry D Jampel

• Drafting the review or commenting on it critically for intellectual content: Fasika A Woreta, Tahreem A Mir, Henry D Jampel

• Final approval of the document to be published: Fasika A Woreta, Tahreem A Mir, Henry D Jampel

Sources of support

Internal sources

• No sources of support supplied

External sources

• Cochrane Eyes and Vision US Project, supported by cooperative agreement 1 U01 EY020522, 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 National Institute for Health Research 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 and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Declarations of interest

Fasika A Woreta: none known. Tahreem A Mir: none known. Henry D Jampel: none known.

New