Topical mydriatics as adjunctive therapy for traumatic iridocyclitis and iritis

Abstract

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

To evaluate the effectiveness and safety of topical mydriatics as adjunctive therapy to topical corticosteroids for traumatic iridocyclitis and iritis.

Background

Description of the condition

Ocular trauma

Hospital emergency department visits for eye‐related complaints are common. Eye trauma accounts for 3% of all emergency department visits in the USA (Romaniuk 2013), with an estimated average of 2.4 million visits for ocular complaints occurring annually (Brandt 2001; Haring 2016). The admission rate for eye injuries has been estimated as 3.1% of emergency department visits, compared with 8.1% for all other types of trauma (Owens 2011). The typical individual experiencing ocular trauma is a twenty year old man. (Haring 2016; May 2000).

The types and patterns of ocular injury present differently, depending on whether the trauma is blunt or penetrating. The most common mechanisms of ocular injury are blunt trauma (30%) and sharp objects (18%); in terms of specific events, motor vehicle collisions account for 9% of ocular injuries and gunshot wounds account for 6% (May 2000). Most ocular injuries occur in the home (41%), whereas 14% occur in the industrial setting (May 2000).

Eye injuries can lead to significant changes in a individual's life in terms of morbidity and quality of life. Although eyes represent only 0.3% of a person's total body surface area, the loss of one eye leads to approximately 24% of whole‐person impairment (i.e. significant malfunction, loss, or loss of use), whereas the loss of both eyes leads to 85% disability (Brandt 2001).

Traumatic iridocyclitis

One consequence of ocular trauma is traumatic iridocyclitis, which is associated with significant morbidity and vision loss when not recognized and managed properly. Iridocyclitis can develop even after minor non‐penetrating ocular trauma. Reported rates of traumatic iridocyclitis range from 0.4% to 49%. Differences in time periods, geographic locations, and surveillance methodology and countries' income level account for the variability in rates reported (London 2010; Macewen 1989; Oner 2006; Soliman 2008).

Traumatic iridocyclitis is one of the most common etiologies of non‐infectious uveitis. Engelhard 2015a reported that 12.2% of all uveitis cases were attributed to trauma during a 30‐year surveillance period. Of note, most uveitis cases (25.7%) have been found to be idiopathic (Bajwa 2015).

Children are an important subgroup of individuals who suffer ocular trauma, and experience greater morbidity from traumatic iridocyclitis. Children represent a diagnostic challenge because of their inability to communicate their symptoms and to comply with the required physical examination (Engelhard 2015a). Traumatic iridocyclitis is one of the most common identifiable reasons for uveitis in this age group, along with juvenile idiopathic arthritis (JIA) and undifferentiated causes (Engelhard 2015b). Traumatic iridocyclitis represents about 25% of all pediatric non‐JIA uveitis (Engelhard 2015b), with a prevalence of 9.1% (BenEzra 2005).

Presentation and diagnosis

The pathophysiology of traumatic iridocyclitis involves an unmasking or worsening of an underlying inflammatory process arising from a systemic or infectious cause (Sepah 2013). As the anterior chamber fills with white blood cells and pigmented cells, individuals describe a dull or aching eye pain, photophobia, diminished vision, and tearing within three days of the eye injury (Logothetis 2014). Traumatic iridocyclitis presents as a red eye, characterized by ciliary flush, cells, and flare in the anterior chamber, and poorly dilated pupils (miosis). Other findings include alterations in intraocular pressure (IOP), mydriasis, miosis, conjunctival injection surrounding the limbus, decreased vision, and floaters.

The symptoms and physical findings are a result of ciliary spasms, which cause inflammation of the iris dilator muscle and the iris sphincter. Inflammation of the iris can cause the iris to tear, cut, and bruise, and can increase IOP. Damage to the ciliary body can lead to accumulation of debris in the trabecular meshwork (Dunn 2015). Cataracts, glaucoma, and retinal detachment are possible complications of traumatic iridocyclitis.

Description of the intervention

The standard therapy for traumatic iridocyclitis, the application of topical corticosteroids, acts by reducing the cyclo‐oxygenase inflammatory response (inflammation associated with increased blood flow). Mydriatic agents usually are applied topically to make the pupil dilate by one of two mechanisms: by either temporarily paralyzing the iris sphincter muscles (parasympathetic antagonists) or stimulating the iris dilator muscle (sympathetic agonists). Parasympathetic antagonists (e.g. tropicamide) tend to have a longer duration of action than sympathetic agonists (e.g. phenylephrine).

How the intervention might work

The adjuvant use of topical mydriatic agents, also administered topically, may help to stabilize blood flow and additionally mitigate ciliary spasm by paralyzing the iris and ciliary body. In addition, mydriatic agents may prevent iris‐lens adhesions (i.e. posterior synechiae) by keeping the iris dilated and minimize contact between them. The net effect is reducing pain and discomfort and shortening the duration of ciliary spasms.

Why it is important to do this review

There is clinical uncertainty as to the benefits versus harms for the use of adjunctive topical mydriatics. Given how significant ocular pain and diminished visual acuity can occur with traumatic iridocyclitis, it is important to evaluate the role of adjunctive topical mydriatics in the management of this condition. No previous systematic review has been conducted on this topic to date.

Objectives

To evaluate the effectiveness and safety of topical mydriatics as adjunctive therapy to topical corticosteroids for traumatic iridocyclitis and iritis.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomized controlled trials (RCTs). The primary intervention group in eligible trials will have received topical mydriatic agents in conjunction with topical corticosteroids. The comparison group will have been treated with topical corticosteroids alone. We will exclude cross‐over trials, within‐person trials, and N‐of‐1 trials (single person clinical trials).

Types of participants

We will include trials that enrolled participants of any age with traumatic iridocyclitis or iritis. We will exclude trials that enrolled participants with open globe injuries or injuries that involved the posterior segments of the eye because these injuries require surgical intervention.

Types of interventions

The intervention that is the focus of this review will be topical mydriatic agents combined with topical corticosteroids. The control intervention to which it will be compared will be topical corticosteroids alone, regardless of dose, frequency, or length of administration. We will exclude placebo‐controlled trials, with the exception of multi‐armed trials in which outcomes for the two targeted interventions are reported separately.

Types of outcome measures

Primary outcomes

• Proportion of participants with resolution of signs and symptoms at one week after treatment, as defined by trial investigators. Typical definitions of resolution include absence of signs (anterior chamber cells, ciliary flushing) and symptoms (ocular pain, floaters).

Secondary outcomes

• Proportion of participants with resolution of signs and symptoms at two weeks and one month after treatment, as defined by trial investigators.

• Proportion of participants with ocular pain at one week, two weeks, and one month after treatment, as defined by trial investigators.

• Proportion of participants with evidence of ocular inflammation (such as cells in the anterior chamber, ciliary flushing, and floaters) at one week, two weeks, and one month after treatment, as defined by trial investigators.

• Proportion of participants with synechiae at one week, two weeks, and one month after treatment, as defined by trial investigators.

• Mean change in best‐corrected visual acuity (BCVA) from baseline to one week, two weeks, and one month after treatment, as defined by trial investigators. When possible we will use logMAR visual acuity values, with Early Treatment Diabetic Retinopathy Study (ETDRS) letters or logMAR acuity of 0.1 considered to be a clinically meaningful difference.

• Mean change in IOP from baseline to one week, two weeks, and one month after treatment, as defined by trial investigators. We will consider 2 mmHg to be a clinically meaningful difference.

If mean change from baseline data are not available for BCVA or IOP outcomes, we will calculate the mean difference in measurements taken at each time point to estimate between‐group effects.

Adverse events

We will compare the proportion of participants with serious ocular adverse events, such as blindness and chronic pain, and systemic adverse events between the two groups at one week, two weeks, and one month after treatment. We will include both spontaneously reported and systematically collected adverse events.

Search methods for identification of studies

Electronic searches

We will search the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision (CEV) Trials Register (latest issue), Ovid MEDLINE, Ovid MEDLINE E‐pub Ahead of Print, Ovid Medline In‐Process and Other Non‐Indexed Citations, Ovid MEDLINE Daily (January 1946 to present), Embase (January 1947 to present), CINAHL Plus (January 1937 to present), PubMed (January 1948 to present), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) to identify potentially eligible studies for this review. We will not use any date or language restrictions in the electronic search for trials.

See the Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), Embase (Appendix 3), CINAHL (Appendix 4), PubMed (Appendix 5), ClinicalTrials.gov (Appendix 6), and the WHO ICTRP (Appendix 7).

Searching other resources

We will search the reference lists of review articles, relevant trials, and textbooks to identify additional trials. We will not impose any language restrictions.

Data collection and analysis

Selection of studies

Two review authors (JH and MK) will independently screen the titles and abstracts of all records and assess the relevance of each. We will obtain full‐text copies of reports from potentially relevant studies. Two review authors (JH and MK) will independently assess the full‐text reports to determine the eligibility of studies for inclusion in the review. The review authors will be unmasked to the trial authors, institution, and trial results during the assessment. At all stages, we will resolve any discrepancies by discussion or by consulting a third review author (SS) whenever necessary. We will list the excluded studies and their reasons for exclusion in the ‘Characteristics of excluded studies' table. We will illustrate the study selection process in a PRISMA diagram.

Data extraction and management

Two review authors (JH and YS) will independently extract data from each eligible study using forms developed and piloted for CEV. We will extract and enter the following information into a systematic review data repository (see also Appendix 8).

• Study characteristics: country, setting, publication year, status of publication, title, authors, source, language of publication, and funding sources.

• Methods: study duration, randomization technique, allocation concealment method, masking (participants, provider, outcome assessors), analysis (intention‐to‐treat versus per protocol or other).

• Participants: source, sampling (random or convenience), number in comparison groups, age, gender, similarity of groups at baseline, withdrawals/losses to follow‐up (reasons), and subgroups for which outcomes were reported.

• Interventions: description of adjuvant mydriatics used plus topical corticosteroids and topical corticosteroids alone (dose and duration).

• Outcomes: primary and secondary outcomes, times of assessment, and length of participant follow‐up (planned and actual).

Whenever outcome data are shown only in figures (e.g. means and standard deviations) we will use GetData Graph Digitizer 2.24 (getdata‐graph‐digitizer.com) to estimate data values from the figures. We will request confirmation from study investigators. If they do not reply within two weeks, we will use the data values we estimate.

Assessment of risk of bias in included studies

Two review authors (JH and MK) will independently assess the risk of bias for each included trial according to Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will assess risk of bias using domain‐based evaluations regarding selection bias (random sequence generation, allocation concealment before randomization), performance bias (masking of participants and study personnel), detection bias (masking of outcome assessors), attrition bias (amount and appropriate handling of missing data), reporting bias (lack of selective outcome reporting), and other potential sources of bias. We will judge each trial for each ‘Risk of bias' domain as ‘low risk', ‘high risk', or ‘unclear risk'.

Measures of treatment effect

We will analyze dichotomous outcomes as risk ratios with 95% confidence intervals (CIs). Dichotomous outcomes for this review include the proportion of participants with resolution of signs and symptoms, the proportion of participants with ocular pain, the proportion of participants with evidence of ocular inflammation, the proportion of participants with synechiae, and the proportion of participants with serious ocular or systemic adverse events.

We will analyze continuous outcomes as mean differences with 95% CIs. We will analyze the mean change in BCVA and IOP as continuous outcomes.

Unit of analysis issues

The ideal unit of analysis will be the individual, such as when trial participants had only one eye affected or when both affected eyes were treated in the same way and analyzed as a unit. We will exclude within‐person studies in which both participants' (affected) eyes were randomized separately.

If we identify eligible multi‐arm trials, we will provide study characteristics for all group and include only relevant groups for analysis without double‐counting of participants.

Dealing with missing data

We will contact the trial authors to obtain supplemental information on missing data. When no response is received within two weeks of the request, we will use the information as available in the study reports.

We will not impute data for the purposes of this review; however, when imputed outcome data are reported in the trial reports, we will use the imputed data reported by the trial investigators. We will perform a sensitivity analysis in which we will exclude studies with high attrition rates (greater than 20%).

Assessment of heterogeneity

We will assess clinical and methodological heterogeneity among included trials to determine whether meta‐analysis is appropriate. When substantial clinical or methodological heterogeneity is observed, we will present a narrative summary of the trial results. When trials are clinically and methodologically homogeneous, we will combine data using meta‐analysis and evaluate statistical heterogeneity using a Chi² test (with a 10% level of statistical significance), the I² statistic (≥ 50% representing substantial statistical heterogeneity), and examination of forest plots for overlapping CIs (Deeks 2011).

Assessment of reporting biases

We will assess small study effects using funnel plots when 10 or more trials are included in a meta‐analysis. An asymmetrical funnel plot may be the result of reporting bias, heterogeneity, and differences in the methodological quality of studies. We will assess selective outcome reporting as part of our assessment of the risk of bias among included studies.

Data synthesis

We will analyze outcome data using Review Manager 5 (RevMan 2014). We will conduct meta‐analyses using the random‐effects model unless there are fewer than three trials, in which case we will use the fixed‐effect model.

Subgroup analysis and investigation of heterogeneity

Whenever sufficient data have been reported, we will perform subgroup analyses according to the following participant and treatment characteristics: age (less than 18 years, 18 years or older) and level and type of injury (Glasgow coma scale, other trauma severity score, blunt injury, etc.). We will investigate differences between subgroups using tests for interaction (P < 0.1, defined as indication treatment‐characteristic interaction). We also will report any post‐hoc subgroup analyses and the number of analyses performed.

Sensitivity analysis

We will examine the impact of excluding studies at high risks of selection, detection and attrition biases, studies providing only unpublished data, and industry‐funded studies in sensitivity analyses whenever sufficient data are available.

‘Summary of findings' table

We will construct a ‘Summary of findings' table that will include effect estimates for the following primary outcome and key secondary outcomes.

• Proportion of participants with resolution of signs and symptoms at one week after treatment, as defined by trial investigators.

• Proportion of participants with ocular pain at one week after treatment, as defined by trial investigators.

• Proportion of participants with evidence of ocular inflammation (such as cells in the anterior chamber, ciliary flushing, and floaters) at one week after treatment, as defined by trial investigators.

• Proportion of participants with synechiae at one week after treatment, as defined by trial investigators.

• Mean change in BCVA from baseline to one week after treatment, as defined by trial investigators.

• Mean change in IOP from baseline to one week after treatment, as defined by trial investigators.

• Proportion of participants with serious ocular adverse events at one week after treatment.

We will use the GRADE approach and its five major domains ‐ risk of bias, inconsistency, directness, imprecision, and publication bias ‐ to provide a strength of evidence rating (very low, low, medium, high) for each outcome included in the ‘Summary of findings' table (Schünemann 2011).

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Uveitis] explode all trees #2 Iridocycliti* #3 iritis* or iritide* #4 Cycliti* #5 scleriti* #6 uveiti* #7 (sclera or iris or ciliary) and (inflam*) #8 {or #1‐#7} #9 MeSH descriptor: [Mydriatics] explode all trees #10 mydriatic* #11 cycloplegic* #12 MeSH descriptor: [Atropine] explode all trees #13 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" #14 berefrine or POPD or "105567‐83‐7" #15 MeSH descriptor: [Cyclopentolate] explode all trees #16 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" #17 MeSH descriptor: [Epinephrine] explode all trees #18 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" #19 MeSH descriptor: [Ethylmorphine] explode all trees #20 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" #21 Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6" #22 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" #23 MeSH descriptor: [Hyoscyamine] explode all trees #24 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" #25 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" #26 Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4" #27 MeSH descriptor: [Naphazoline] explode all trees #28 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" #29 Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5" #30 MeSH descriptor: [Synephrine] explode all trees #31 MeSH descriptor: [Oxyphenonium] explode all trees #32 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" #33 MeSH descriptor: [Phenylephrine] explode all trees #34 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" #35 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" #36 MeSH descriptor: [p‐Hydroxyamphetamine] explode all trees #37 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" #38 MeSH descriptor: [Racepinephrine] explode all trees #39 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" #40 MeSH descriptor: [Scopolamine Hydrobromide] explode all trees #41 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 hyscoor "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" #42 MeSH descriptor: [Tropicamide] explode all trees #43 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" #44 MeSH descriptor: [Tyramine] explode all trees #45 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" #46 Vibrocil or "8059‐14‐1" #47 MeSH descriptor: [Yohimbine] explode all trees #48 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" #49 {or #9‐#48} #50 #8 and #49

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 Uveitis/ 13. Iridocycliti*.tw. 14. (iritis* or iritide*).tw. 15. Cycliti*.tw. 16. scleriti*.tw. 17. uveiti*.tw. 18. ((sclera or iris or ciliary) and inflam*).tw. 19. or/12‐18 20. exp Mydriatics/ 21. mydriatic*.tw. 22. cycloplegic*.tw. 23. exp Atropine/ 24. (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. 25. ("51‐55‐8" or "55‐48‐1").rn. 26. (berefrine or POPD or "105567‐83‐7").tw. 27. "105567‐83‐7".rn. 28. exp Cyclopentolate/ 29. (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. 30. ("512‐15‐2" or "5870‐29‐1").rn. 31. exp Epinephrine/ 32. (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").tw. 33. ("51‐43‐4" or "55‐31‐2" or "6912‐68‐1").rn. 34. exp Ethylmorphine/ 35. (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. 36. ("125‐30‐4" or "76‐58‐4").rn. 37. (Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6").tw. 38. ("100‐91‐4" or "536‐93‐6").rn. 39. (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. 40. ("51‐56‐9" or "87‐00‐3").rn. 41. exp Hyoscyamine/ 42. (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. 43. ("101‐31‐5" or "306‐03‐6").rn. 44. (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. 45. ("66195‐31‐1" or "75011‐65‐3").rn. 46. (Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4").tw. 47. "31610‐87‐4".rn. 48. exp Naphazoline/ 49. (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. 50. ("5144‐52‐5" or "550‐99‐2" or "835‐31‐4").rn. 51. (Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5").tw. 52. "94‐07‐5".rn. 53. exp Synephrine/ 54. exp Oxyphenonium/ 55. (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. 56. ("14214‐84‐7" or "50‐10‐2").rn. 57. exp Phenylephrine/ 58. (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").tw. 59. ("532‐38‐7" or "59‐42‐7" or "61‐76‐7").rn. 60. (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. 61. "370‐14‐9".rn. 62. exp p‐Hydroxyamphetamine/ 63. (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. 64. ("103‐86‐6" or "1518‐86‐1" or "306‐21‐8").rn. 65. exp Racepinephrine/ 66. (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").tw. 67. "329‐65‐7".rn. 68. exp Scopolamine Hydrobromide/ 69. (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").tw. 70. ("114‐49‐8" or "138‐12‐5" or "51‐34‐3" or "55‐16‐3").rn. 71. exp Tropicamide/ 72. (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. 73. "1508‐75‐4".rn. 74. exp Tyramine/ 75. (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. 76. ("51‐67‐2" or "60‐19‐5").rn. 77. (Vibrocil or "8059‐14‐1").tw. 78. "8059‐14‐1".rn. 79. exp Yohimbine/ 80. (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. 81. ("146‐48‐5" or "65‐19‐0").rn. 82. or/20‐81 83. 19 and 82 84. 11 and 83

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

Appendix 3. Embase 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 'uveitis'/exp #34 Iridocycliti*:ti,ab #35 (iritis* OR iritide*):ti,ab #36 Cycliti*:ti,ab #37 scleriti*:ti,ab #38 uveiti*:ti,ab #39 ((sclera OR iris OR ciliary) AND inflam*):ti,ab #40 #33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 #41 'mydriatic agent'/exp #42 mydriatic*:ti,ab #43 cycloplegic*:ti,ab #44 (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 #45 (berefrine OR POPD OR "105567‐83‐7"):ab,ti,tn #46 (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 #47 'epinephrine'/exp #48 (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 #49 (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 #50 (Eucatropine OR euphthalmine OR "100‐91‐4" OR "536‐93‐6"):ab,ti,tn #51 (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 #52 'hyoscyamine'/exp #53 (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 #54 'ibopamine'/exp #55 (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 #56 (Methylatropine OR "8‐methylatropinium nitrate" OR "31610‐87‐4"):ti,ab,tn #57 (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 #58 (Oxedrine OR Synephrine OR Sympaethamin OR Synephrin OR aetaphen OR pentedrine OR vasoton OR "94‐07‐5"):ti,ab,tn #59 'oxyphenonium bromide'/exp #60 (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 #61 (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 #62 (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 #63 'hydroxyamphetamine'/exp #64 (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 #65 'racepinefrine'/exp #66 (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 #67 'scopolamine bromide'/exp #68 (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 #69 (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 #70 (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 #71 (Vibrocil OR "8059‐14‐1"):ti,ab,tn #72 'yohimbine'/exp #73 (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 #74 #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 #75 #40 AND #74 #76 #32 AND #75

Appendix 4. CINAHL search strategy

S1 (MH "Uveitis+") S2 TI Iridocycliti* OR AB Iridocycliti* S3 TI ( iritis* or iritide* ) OR AB ( iritis* or iritide*) S4 TI Cycliti* OR AB Cycliti* S5 TI scleriti* OR AB scleriti* S6 TI uveiti* OR AB uveiti* S7 TI ( (sclera or iris or ciliary) and (inflam*) ) OR AB ( (sclera or iris or ciliary) and (inflam*) ) S8 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 S9 (MH "Mydriatics+") S10 TI mydriatic* OR AB mydriatic* S11 TI cycloplegic* OR AB cycloplegic* S12 TI ( 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" ) OR AB ( 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" ) S13 TI (berefrine or POPD or "105567‐83‐7") OR AB (berefrine or POPD or "105567‐83‐7") S14 TI (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") OR AB (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") S15 TI (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") OR AB (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") S16 TI (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") OR AB (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") S17 TI (Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6") OR AB (Eucatropine or euphthalmine or "100‐91‐4" or "536‐93‐6") S18 TI (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) OR AB (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) S19 TI (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") OR AB (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") S20 TI (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") OR AB (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") S21 TI (Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4") OR AB (Methylatropine or "8‐methylatropinium nitrate" or "31610‐87‐4") S22 TI (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") OR AB (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") S23 TI (Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5") OR AB (Oxedrine or Synephrine or Sympaethamin or Synephrin or aetaphen or pentedrine or vasoton or "94‐07‐5") S24 TI (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") OR AB (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") S25 TI (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") OR AB (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") S26 TI (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") OR AB (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") S27 TI (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") OR AB (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") S28 TI (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") OR AB (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") S29 TI (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") OR AB (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") S30 TI (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") OR AB (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") S31 TI (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") OR AB (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") S32 TI (Vibrocil or "8059‐14‐1") OR AB (Vibrocil or "8059‐14‐1") S33 (MH "Yohimbine") S34 TI (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") OR AB (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") S35 (S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32 OR S33 OR S34) S36 S8 AND S35

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

Appendix 6. ClinicalTrials.gov search strategy

(cyclopegics is synonym for mydriatics, racepinephrine is synonym for epinephrine)

(uveitis OR iridocyclitis OR iritis OR iritides OR cyclitis OR scleritis) AND (mydriatics OR atropine OR berefrine OR cyclopentolate OR epinephrine OR ethylmorphine OR eucatropine OR homatropine OR hyoscyamine OR ibopamine OR oxyphenonium)

(uveitis OR iridocyclitis OR iritis OR iritides OR cyclitis OR scleritis) 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

uveitis AND mydriatics OR uveitis AND cycloplegics OR uveitis AND atropine OR uveitis AND berefrine OR uveitis AND cyclopentolate OR uveitis AND epinephrine OR uveitis AND ethylmorphine OR uveitis AND eucatropine OR uveitis AND homatropine OR uveitis AND hyoscyamine OR uveitis AND ibopamine OR uveitis AND oxyphenonium OR uveitis AND methylatropine OR uveitis AND naphazoline OR uveitis AND oxedrine OR uveitis AND p‐hydroxyamphetamine OR uveitis AND phenylephrine OR uveitis AND pholedrine OR uveitis AND racepinephrine OR uveitis AND scopolamine OR uveitis AND tropicamide OR uveitis AND tyramine OR uveitis AND vibrocil OR uveitis AND yohimbine

iridocyclitis AND mydriatics OR iridocyclitis AND cycloplegics OR iridocyclitis AND atropine OR iridocyclitis AND berefrine OR iridocyclitis AND cyclopentolate OR iridocyclitis AND epinephrine OR iridocyclitis AND ethylmorphine OR iridocyclitis AND eucatropine OR iridocyclitis AND homatropine OR iridocyclitis AND hyoscyamine OR iridocyclitis AND ibopamine OR iridocyclitis AND oxyphenonium OR iridocyclitis AND methylatropine OR iridocyclitis AND naphazoline OR iridocyclitis AND oxedrine OR iridocyclitis AND p‐hydroxyamphetamine OR iridocyclitis AND phenylephrine OR iridocyclitis AND pholedrine OR iridocyclitis AND racepinephrine OR iridocyclitis AND scopolamine OR iridocyclitis AND tropicamide OR iridocyclitis AND tyramine OR iridocyclitis AND vibrocil OR iridocyclitis AND yohimbine

iritis AND mydriatics OR iritis AND cycloplegics OR iritis AND atropine OR iritis AND berefrine OR iritis AND cyclopentolate OR iritis AND epinephrine OR iritis AND ethylmorphine OR iritis AND eucatropine OR iritis AND homatropine OR iritis AND hyoscyamine OR iritis AND ibopamine OR iritis AND oxyphenonium OR iritis AND methylatropine OR iritis AND naphazoline OR iritis AND oxedrine OR iritis AND p‐hydroxyamphetamine OR iritis AND phenylephrine OR iritis AND pholedrine OR iritis AND racepinephrine OR iritis AND scopolamine OR iritis AND tropicamide OR iritis AND tyramine OR iritis AND vibrocil OR iritis AND yohimbine

iritides AND mydriatics OR iritides AND cycloplegics OR iritides AND atropine OR iritides AND berefrine OR iritides AND cyclopentolate OR iritides AND epinephrine OR iritides AND ethylmorphine OR iritides AND eucatropine OR iritides AND homatropine OR iritides AND hyoscyamine OR iritides AND ibopamine OR iritides AND oxyphenonium OR iritides AND methylatropine OR iritides AND naphazoline OR iritides AND oxedrine OR iritides AND p‐hydroxyamphetamine OR iritides AND phenylephrine OR iritides AND pholedrine OR iritides AND racepinephrine OR iritides AND scopolamine OR iritides AND tropicamide OR iritides AND tyramine OR iritides AND vibrocil OR iritides AND yohimbine

cyclitis AND mydriatics OR cyclitis AND cycloplegics OR cyclitis AND atropine OR cyclitis AND berefrine OR cyclitis AND cyclopentolate OR cyclitis AND epinephrine OR cyclitis AND ethylmorphine OR cyclitis AND eucatropine OR cyclitis AND homatropine OR cyclitis AND hyoscyamine OR cyclitis AND ibopamine OR cyclitis AND oxyphenonium OR cyclitis AND methylatropine OR cyclitis AND naphazoline OR cyclitis AND oxedrine OR cyclitis AND p‐hydroxyamphetamine OR cyclitis AND phenylephrine OR cyclitis AND pholedrine OR cyclitis AND racepinephrine OR cyclitis AND scopolamine OR cyclitis AND tropicamide OR cyclitis AND tyramine OR cyclitis AND vibrocil OR cyclitis AND yohimbine

scleritis AND mydriatics OR scleritis AND cycloplegics OR scleritis AND atropine OR scleritis AND berefrine OR scleritis AND cyclopentolate OR scleritis AND epinephrine OR scleritis AND ethylmorphine OR scleritis AND eucatropine OR scleritis AND homatropine OR scleritis AND hyoscyamine OR scleritis AND ibopamine OR scleritis AND oxyphenonium OR scleritis AND methylatropine OR scleritis AND naphazoline OR scleritis AND oxedrine OR scleritis AND p‐hydroxyamphetamine OR scleritis AND phenylephrine OR scleritis AND pholedrine OR scleritis AND racepinephrine OR scleritis AND scopolamine OR scleritis AND tropicamide OR scleritis AND tyramine OR scleritis AND vibrocil OR scleritis AND yohimbine

Appendix 8. Data on study characteristics

Mandatory items		Optional items
Methods
Study design	Parallel‐group randomized controlled trial (RCT) i.e. people randomized to treatment Within‐person RCT i.e. eyes randomized to treatment Cluster RCT i.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 of 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 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= )	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	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

JH: conception and design of study, drafting the review, final approval of the document published. SS: design of study, drafting the review, final approval of the document published. MK: design of study, commenting on the review, final approval of the document published. CM: design of study, commenting on the review, final approval of the document published. YS: design of study, commenting on the review, final approval of the document published. QN: design of study, commenting on the review, final approval of the document published.

Sources of support

Internal sources

• None, Other.

External sources

• Methodological support provided by the CEV US Project, supported by grant 5 UG1 EY020522, National Eye Institute, National Institutes of Health, USA.

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

  • Richard Wormald, Co‐ordinating Editor for the Cochrane Eyes and Vision Group (CEVG) acknowledges financial support for his CEVG 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 authors and not necessarily those of the NIHR, NHS, or the Department of Health.

Declarations of interest

JH: none known. SS: none known. MK: none known. CM: none known. YS: none known. QN: has received grants and other financial support from Genentech, Regeneron, AbbVie, Psivida, XOMA, Santen, Allergan, and Heidelberg. However, none of these are relevant to the current Cochrane Review.

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