Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Alhassan, 2015

[individual study characteristics deduced from [Alhassan, 2015]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCT’s

Literature search up to March 2015

A: Ali-Melkkila, 1992

B: Ali-Melkkila, 1993

C: Athanikar, 1991

D: Feibel, 1993

E: Weiss, 1989

F: Wong, 1993

Study design: RCT parallel

Setting and Country: hospital-based settings in Finland (A,B), India (C), USA (D, E) and Canada (F)

Source of support:

National Eye Centre, Kaduna, Nigeria; Cochrane Anaesthesia Review Group, Denmark; UK Cochrane Centre, UK; Cochrane Eye and Vision Group, UK.

Inclusion criteria SR: RCT’s in which a comparison was made between peribulbar block and retrobulbar

block for cataract surgery.

Exclusion criteria SR: trials comparing peribulbar or retrobulbar

anaesthesia with any others forms of anaesthesia for cataract surgery; trials in which cataract surgery was combined

with any other ocular surgery

6 studies included

Important patient characteristics at baseline:

 n= 1438 included participants; characteristics not described

N, mean age

A: n=300, 68 yrs

B: n=450, ? yrs

C: n=142, ? yrs

D: n=317, ? yrs

E: n=79 , ? yrs

F: n=150, age range21-95 yrs

Sex: not reported

Groups comparable at baseline?

No information

Describe intervention:

Peribulbar block

A: periocular anesthesia

B: periocular anesthesia

C: one point low volume peribulbar anaesthesia

D: periocular anesthesia

E: periocular anesthesia

F: peribulbar anesthesia

Describe control:

Retrobulbar block

A: retrobulbar anesthesia

B: retrobulbar anesthesia

C: retrobulbar anesthesia

D: retrobulbar anesthesia

E: retrobulbar anesthesia

F: retrobulbar anesthesia or modified retrobulbar anesthesia

End-point of follow-up: during time of surgery for five included RCT’s , only one RCT evaluated persistent ptosis at 90 days after surgery

A, B, C, E, F: no follow-up beyond surgery

D: 90 days after surgery

For how many participants were no complete outcome data available?

(intervention/control)

Complete outcome data in all included RCT’s

Pain score

Defined as pain experienced during surgery and measured using a visual analogue scale (VAS) (1 to 10) or any other method as described in the primary report.

Mean difference [95% CI]:

C:: -0.05 [ -0.19, 0.09]

E: 0.14 [ -0.31, 0.59]

Pooled effect (fixed effect model): -0.03 [ -0.17, 0.11] Heterogeneity (I2): 0%

Globe akinesia

Defined as the degree to which the ocular muscles were paralysed and the eye immobilized, i.e. complete akinesia.

Risk ratio [95% CI]

A: 0.79 [ 0.65, 0.94 ]

B: 1.04 [ 0.92, 1.18 ]

C: 1.00 [ 0.97, 1.03 ]

D: 1.03 [ 0.94, 1.13 ]

Pooled effect (random effects model): 0.98 [ 0.88, 1.09 ]

Heterogeneity (I2): 81%

Need for additional injection

Defined as the number of additional injections (of local anaesthetic) given in order to achieve good akinesia.

Risk ratio [95% CI]

A: 2.78 [ 1.74, 4.43 ]

B: 1.22 [ 0.73, 2.04 ]

E: 1.41 [ 0.64, 3.13 ]

F: 0.88 [ 0.34, 2.27 ]

Pooled effect (random effects model): 1.54 [ 0.91, 2.60 ]

Heterogeneity (I2): 62%

Local complications

Defined as the number of participants in whom local complications were observed during or after administration of a local anaesthetic

Risk ratio [95% CI]

Retrobulbar haemorrhage

C: 0.33 [ 0.01, 8.05 ]

Conjunctival chemosis

A: 3.12 [ 1.15, 8.43 ]

B: 1.63 [ 1.02, 2.58 ]

C: 11.00 [ 1.46, 82.96 ]

F: 2.00 [ 0.80, 5.02 ]

Pooled effect (random effects model): 2.11 [ 1.46, 3.05 ] favoring retrobulbar

Heterogeneity (I2): 32%

Lid haematoma

B: 0.36 [ 0.15, 0.88 ]

Ptosis

D: 1.06 [ 0.43, 2.60 ]

Systemic complications

Defined as the number of participants in whom systemic complications arose during or after administration of a local anaesthetic (examples include respiratory depression, cardiopulmonary arrest).

“No major systemic complications were reported in any of the trials”

Acceptability of blocks

Defined as the number of participants who reported that the blocks were acceptable to them.

Risk ratio [95% CI]

B: 1.02 [ 0.99, 1.04 ]

F: 0.97 [ 0.88, 1.06 ]

Pooled effect (random effects model): 1.01 [ 0.98, 1.03 ]

Heterogeneity (I2): 35%

Brief description of author’s conclusion: “There is little to choose between peribulbar and retrobulbar block in terms of anaesthesia and akinesia during surgery measuring

acceptability to patients, need for additional injections and development of severe complications. Severe local or systemic complications

were rare for both types of block.”

Methodological quality of SR was good. Publication bias was not explicitly mentioned, however, GRADE was applied of which one of the domains is publication bias. There was no downgrading for publication bias. Conflict of interest was not reported for the included RCT’s .

Methodological quality of included RCT’s : three of the included six trials had adequate sequence generation while it was unclear for all trials whether allocation had been concealed. There was a low risk on performance bias, detection bias and selective reporting.

Level of evidence: GRADE (per outcome measure)

Pain score: low

Globe akinesia: low

Need for additional injection: low

Local complications: moderate

Acceptability of blocks: moderate

Reasons for downgrading were because of (very) serious limitations in study design.

Most outcomes presented were during the operation, no postoperative follow-up.

Guay, 2015

[individual study characteristics deduced from Guay, 2015

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCT’s

Literature search up to November 2014

A: Adams, 2008

B: Chittenden, 1997

C: Mathew, 2003

D: Rüschen, 2005

E: Sekundo, 2004

F: Srinivasan, 2004

G: Vielpeau, 1999

H: Zafirakis, 2001

Study design: 5 parallel RCT’s (B, C, D, E, F) and 2 cross-over RCT’s (G, H) analysed.

Data-extraction not possible for 1 RCT (A)

Setting and Country: not reported

Source of funding:

University of Sherbrooke, Canada, and University of Quebec in Abitibi-Temiscamingue, Canada, for access to medical journals;

Cochrane Anaesthesia Review Group, Denmark, for search strategy and list of abstracts

Inclusion criteria SR: RCT’s comparing topical anaesthesia with or without intracameral injection versus

sub-Tenon’s anaesthesia in adult patients undergoing cataract surgery on one eye or on both eyes, provided that the anaesthetic technique for the first eye was chosen at random

Exclusion criteria SR: studies in which participants received intravenous sedation

8 studies included, 7 analysed

Important patient characteristics at baseline:

N=617 participants included (742 operated eyes)

N, mean age

A: n=205

B: n=35

C: n=119

D: n=28

E: n=100

F: n=210

G: n=25 (cross-over)

H: n=100 (cross-over)

Mean age of participants in included RCT’s varied from71.5 years to 83.5 years

Sex:

Female proportion of participants in included RCT’s varied from 54% to

76%

Groups comparable at baseline?

No information provided.

Describe intervention: topical anaesthesia with or without intracameral injection

A: topical anaesthesia with oxybuprocaine 0.4% drops

B: topical anaesthesia provided by 0.4% oxybuprocaine hydrochloride (Benoxinate), instilled onto the cornea and the conjunctiva

C: proparacaine 0.5%

D: topical anaesthesia with 2 drops of proxymetacaine 0.5% followed by 4 drops of amethocaine 1% (tetracaine)

E: topical anaesthesia with oxybuprocaine 0.4% 1 drop, xylocaine 2% jelly, 2 applications over 7 to 10minutes, lignocaine 1%1 drop on bare sclera, lignocaine 1% 0.5 mL intracamerally

F: topical anaesthesia with proxymetacaine 0.5% 4+2 drops; 5 minutes apart

G: topical anaesthesia with tetracaine 1% 1+1+1 drop; 10 minutes apart

H: topical anaesthesia with diclofenac 0.1%2+2 drops 20minutes apart, phenylephrine 5% 2+2+2 drops 5 minutes apart, tropicamide 0.5% 2+2+2 drops 5 minutes apart, proparacaine hydrochloride 0.5% 2+2+2+2 drops 3 minutes apart

Describe control:

sub-Tenon’s anaesthesia

A: sub-Tenon’s anaesthesia with lidocaine 2% with 1 in 200,000 epinephrine plus bupivacaine 0.75%

B: Benoxinate drops, small subconjunctival injection of 2% lignocaine with 1:200,000 adrenaline to raise a small bleb; 2 to 3 mL of 2% lignocaine with 1:200,000 adrenaline delivered to the posterior sub-Tenon’s potential space

C: sub-Tenon’s anaesthesia: Lignocaine 2%+ bupivacaine

0.5% or 0.75% + hyaluronidase 3 to 5 mL.

D: sub-Tenon’s anaesthesia with 3 to 4 mL of lidocaine 2%. Local anaesthetic

contained 30 units per millilitre of hyaluronidase.

E: sub-Tenon’s anaesthesia with oxybuprocaine 0.4% 1 drop topically, xylocaine 2% 2 mL

F: sub-Tenon’s anaesthesia with poxymetacaine 0.5% 1 drop topically, lignocaine 2% 2 mL + bupivacaine 0.75% 1 mL

G: sub-Tenon’s with tetracaine 1% 1 drop topically, xylocaine 2% 2 mL

H: sub-Tenon’s anaesthesia with diclofenac 0.1% 2+2 drops 20 minutes apart, phenylephrine 5% 2+2+2 drops 5 minutes apart all topically, lignocaine 2% 0.75

mL + bupivacaine 0.25% 0.75 mL

End-point of follow-up:

A: end of surgery

B: end of surgery

C: end of surgery

D: end of surgery

E: unclear

F: 30 minutes postoperative

G: end of surgery

H: 24 hours postoperative

For how many participants were no complete outcome data available?

(intervention/control)

A: complete outcome data

B: complete outcome data

C: “Two patientswere excluded fromthe study for incomplete data entry”

D: Two of the 28 questionnaires contained

unanswered questions - both in the topical anaesthesia group and were not included in the analysis

E: complete outcome data

F: Nine participants (5 in sub-Tenon’s group and 5 in topical anaesthesia group) were excluded from the analysis, as their pain scores were not recorded

G: complete outcome data

H: complete outcome data

Pain during surgery

Definition not provided.

Standardized mean difference [95% CI]:

B: 1.05 [ 0.34, 1.76 ]

C: 0.81 [ 0.43, 1.19 ]

E: 0.68 [ 0.28, 1.08 ]

F: 0.46 [ 0.16, 0.76 ]

G: 1.02 [ 0.43, 1.61 ]

H: 0.39 [ 0.11, 0.67 ]

Pooled effect (random effects model): 0.64 [ 0.43, 0.84 ]

favoring sub-Tenon’s anaesthesia. With one high-quality trial used as a standard (F; standard deviation (SD) 2.3), this would correspond to a visual/verbal analogical pain scale (VAS) score of 1.5 on a scale from 0 to 10.

Heterogeneity (I²): 36%

Pain during administration of local anaesthetic

Definition not provided

Standardized mean difference [95% CI]

C: -0.11 [ -0.48, 0.26 ]

F: -0.25 [ -0.55, 0.05 ]

Pooled effect (random effects model) of this subgroup of parallel trials: -0.20 [ -0.43, 0.04 ]

H: -2.21 [ -2.57, -1.86 ] favouring topical anaesthesia (cross-over RCT)

No overall pooled effect presented because of heterogeneity (I²): 99%

Postoperative pain at 30 minutes

Definition not provided

Standardized mean difference [95% CI]

F: 0.54 [ 0.24, 0.84 ] favouring sub-Tenon’s anaesthesia (parallel RCT)

H: 0.96 [ 0.67, 1.26 ] favouring sub-Tenon’s anaesthesia (cross-over RCT)

No pooled effect presented because of heterogeneity (I²): 75%

Postoperative pain at 24 hours

Definition not provided

Standardized mean difference [95% CI]

H: -0.47 [ -0.75, -0.19 ] favouring topical anaesthesia

This difference corresponds to 0.2 on a score from 0 to 10 (SD 0.4).

Surgical satisfaction with operating conditions

On a score from 0-10

Mean difference [95% CI]

H: -0.7 [ -0.30, -1.10 ]

favouring sub-Tenon’s anaesthesia

Patient satisfaction with analgesia provided

Definition not provided

Standardized mean difference [95% CI]

D: -1.13 [ -0.30 to -1.96 ]

favouring sub-Tenon’s anaesthesia

Complications that occurred as defined by study authors

Subconjunctival haemorrhage

G: (any amount) 25/25 vs. 25/25

H: 0/100 vs. 22/100, RR= 0.02 [0.00, 0.36]

Chemosis

G: 0/25 vs 15/25, RR= 0.03 [0.00, 0.51]

H: 0/100 vs 76/100, RR= 0.01 [0.00, 0.10]

Transient increase in intraocular pressure

Not reported

Posterior capsular tear

E: 0/50 vs. 0/50

F: 3/65 vs. 2/136, RR= 3.14 [0.54, 18.33]

G: 0/25 vs. 0/25

Iris prolapsus

E: 0/50 vs. 0/50

F: 0/65 vs. 1/136, RR= 0.69 [0.03, 16.76]

G: 0/25 vs. 0/25

Iritis

E: 1/50 vs. 1/50, RR=1.00 [0.06, 15.55]

Brief description of author’s conclusion:

“Both topical anaesthesia and sub-Tenon’s anaesthesia are accepted and safe methods of providing anaesthesia for cataract surgery. An acceptable degree of intraoperative discomfort has to be expected with either of these techniques. Randomized controlled trials on the effects of various strategies to prevent intraoperative pain during cataract surgery could prove useful.”

Methodological quality of SR was good, except that conflict of interest was not reported for the included RCT’s .

Methodological quality of included RCT’s : adequate randomisation and concealment of allocation in two RCT’s , unclear in the other RCT’s ; low risk of performance bias in 2 RCT’s , high in 3, unclear risk in 3. Low risk of detection bias in 5 RCT’s , unclear in 3; low risk of attrition bias in all but 1 RCT; selective reporting in 2 RCT’s .

Level of evidence: GRADE (per outcome measure)

Intraoperative pain: high

Pain during administration of anaesthesia: low (downgraded for study limitations and imprecision)

Pain at 24h: moderate (downgraded for imprecision)

Surgeon’s satisfaction: low (downgraded for imprecision and study limitations)

Participant’s satisfaction: moderate (downgraded for imprecision)

Page, 2009

[individual study characteristics deduced from Page, 2009]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of all study designs

Unclear at which date the literature search was performed. Publication date of most recent included study is 2009

A: Bardocci, 2003

B: Barequet, 1999

C: Busbee, 2008

D: Friedman, 2006

E: Kozak, 2005

F: Li, 2003

G: Oksuz, 2005

H: Oksuz, 2006

I: Rebolleda, 2001

J: Soliman, 2004

K: Theocharis, 2007

L: Thill, 2005

M: Young, 2009

N: Yu, 2003

O: Zabriskie, 2002

P: Assia, 1999

Q: Kwok, 2001

R: Kwok, 2006

S: Lai, 2002

T: Leung, 2006

U: Segev, 2004

V: Miller, 2005

Study design: 15 RCT’s (A-O), 6 nonrandomized prospective studies (P-U), 1 retrospective case series (V), 2 animal studies, 1 microbiologic study and 2 letters to the editor.

Setting and Country: Not reported

Source of funding:

The work was supported in part by an unrestricted grant to Casey Eye Institute from Research to Prevent Blindness, New York, NY.

Inclusion criteria SR: lidocaine gel in ophthalmic surgery

Exclusion criteria SR: Articles on pharmacokinetics, basic physiology, and basic pharmacology

26 studies included

Important patient characteristics at baseline:

N,

A: n=107

B: n=25

C: n=209

D: n=100

E: n=16

F: n=57

G: n=54

H: n=45

I: n=32

J: n=90

K: n=69

L: n=39

M: n=40

N: n=14

O: n=36

P: n=100

Q: n=20

R: n=41

S: n=22

T: n=33

U: n=15

V: n=15920

Mean age and sex: not reported

Groups comparable at baseline?

Not applicable: no meta-analysis because of different indications, interventions and outcomes of the studies included in the review.

Describe intervention:

Lidocaine

Cataract

A: Lidocaine gel 2%

B: Lidocaine gel 2%

J: Lidocaine gel 2%

L: Lidocaine gel 2% + intracameral lidocaine 1%

P: Lidocaine gel 2%

R: Lidocaine gel 2%

V: Lidocaine

Conjunctival pinching

C: Akten 1.5%/2.5%/3.5%

Pterygium excision

G: Lidocaine gel 2%

H: Lidocaine gel 2%, applied regularly in post op period

M: Lidocaine gel 2%

T: Lidocaine gel 2%

PKP

U: Topical lidocaine 2% +

intracameral anesthesia +

iv sedation

Vitreoretinal surgery

D: Lidocaine gel 2%

K: Lidocaine gel 2%

Intravitreal injection

E: Lidocaine gel 2%

Chalazion excision

F: Lidocaine gel 2%

Glaucoma

Ahmed glaucoma implant

I: Lidocaine gel 2%

Trabeculectomy

O: Topical anesthesia

Phaco/trabeculectomy

S: Lidocaine gel 2%

Strabismus

N: Lidocaine gel 2%

Laser procedures

Q: Lidocaine 2%

Describe control:

Other anesthesia

or not applicable (no control group)

Cataract

A: Lidocaine 4% drops

B: Tetracaine drops

J: Bupivacaine 0.5%, benoxinate 0.4%

L: Bupivacaine 0.5% + oxybuprocaine + diclofenac x 4 drops

P: -

R: -

V: -

Conjunctival pinching

C: Sham gel

Pterygium excision

G: Subconjunctival lidocaine 2%

H: Artificial tear gel, applied regularly in postop period

M: Tetracaine drops + solcoseryl eye gel

T: -

PKP

U: -

Vitreoretinal surgery

D: Peribulbar anesthesia

K: Peribulbar anesthesia

Intravitreal injection

E: Subconjunctival lidocaine 2%

Chalazion excision

F: Subconjunctival lidocaine 2%

Glaucoma

Ahmed glaucoma implant

I: retrobulbar injection

Trabeculectomy

O: retrobulbar injection

Phaco/trabeculectomy

S: -

Strabismus

N: Amethocaine 1% in contralateral eye

Laser procedures

Q:-

End-point of follow-up:

A: intraoperative outcomes

B: (directly?) post-surgery

C: intraoperative outcomes

D: unclear, probably intraoperative outcomes

E: unclear, probably intraoperative outcomes

F: intraoperative outcomes

G: intraoperative outcomes

H: 10 hours post-surgery

I: intraoperative outcomes

J: intraoperative outcomes

K: postoperative, time point not mentioned

L: unclear, probably intraoperative outcomes

M: postoperative, time point not mentioned

N: intraoperative outcomes

O: postoperative, time point not mentioned

P: unclear

Q: unclear, probably intraoperative outcomes

R: unclear, probably intraoperative outcomes

S: intraoperative outcomes

T: 15 minutes post-surgery

U: postoperative, time point not mentioned

V: not reported

For how many participants were no complete outcome data available?

not reported

Results presented only for comparisons and studies that are relevant to the guideline under development

Vitreoretinal surgery

Topical vs. peribulbar anesthesia

Pain (VAS)

D: no significant difference in pain between groups, p=0.1

K: no significant difference in pain (intraoperative and postoperative) between groups, p=0.3

terygium excision

Topical anesthesia vs. subconjunctival anesthesia

Pain during administration (VAS)

G: 0.92 ± 0.56 vs. 4.26 ± 1.18, p<0.01

Intraoperative pain

G: 3.96 ± 0.95 vs. 4.0 ± 1.01, p=0.55

Chalazion excision

Topical anesthesia vs. subconjunctival anesthesia

Pain during administration

(verbal pain score, 0-100)

F: 5.5 vs. 47.0, p<0.001

Intraoperative pain

(verbal pain score, 0-100)

F: 48.28 vs. 51.4, p=0.679

“fear of injection”

patient reported, scale 0–100) F: 43.9 vs 47.7, p=0.668)

Facultative:

Brief description of author’s conclusion:

“Lidocaine gel is a safe, effective, and potentially underutilized tool for ophthalmic surgery.”

Methodological quality of SR:

only one database searched and details regarding search period were not provided. No description of excluded studies. Methodological quality of included studies was reported for RCT’s only. Potential risk of publication bias was not assessed and conflict of interest was not reported for the included studies.

Unclear what method was used to assess methodological quality of included studies. The review authors state that:

“Two of the RCT’s were double-blinded;(A,C) the remaining 13 were unblinded but considered to be high-quality with the exception of 2 that were possibly underpowered (N< 20).(E, N) Meta-analysis was not carried out on the studies due to their variable endpoints, differing surgical/procedural environments, and variable

control groups across the studies.

Wang, 2012

[individual study characteristics deduced from Wang, 2012]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCT’s

Literature search up to November 2011

A: Al-Yousuf, 2003

B: Azmon, 1999

C: Budd, 2009

D: Parkar, 2005

E: Ripart, 2000

Study design: RCT [parallel), 1 RCT (C) used paired data comparing one eye of a patient with the other eye of the same patient for each treatment group; all other RCT’s used unpaired data

Setting and Country: hospital based in Bahrain, Israel, United Kingdom, India, France (A, B, C, D and E, respectively)

Source of funding:

authors have no funding or conflicts of interest to declare.

Inclusion criteria SR: randomized controlled trials comparing peribulbar and sub-Tenon anaesthesia for cataract surgery

Exclusion criteria SR: comparison of peribulbar or sub-

Tenon anesthesia with other forms of anaesthesia; cataract surgery combined with other ocular surgery.

5 studies included

Important patient characteristics at baseline:

N=398 patients and 448 eyes

N, mean age

A: n=50, 65 yrs

B: n=64, 68.5 yrs (sub-Tenon) and 65 yrs (peribulbar)

C: 50 (both eyes operated on within 34 days of each other), 78 yrs

D: n=168, 56 yrs (sub-Tenon) and 58 yrs (peribulbar)

E: n=66, 76 yrs (sub-Tenon) and 78 yrs (peribulbar)

Sex (M/F):

A: not reported

B: 28/36

C: 12/38

D: 87/81

E: 25/41

Groups comparable at baseline?

“Groups were similar at the beginning of each study in relation to age and sex, and groups were treated equally in

each study, with the exception of the regional anesthesia technique.”

Describe intervention:

sub-Tenon’s anaesthesia

A: topical 1% amethocaine; 50:50 2% lidnocaine and 0.5% bupivacaine 4 mL (blunt cannula); Honan balloon for 7 min

B: topical 0.4% benoxinate; 50:50 2% lignocaine and 0.5% bupivacaine 2 mL (Visitec cannula)

C: topical 0.5% proxymetacaine and 1% tetracaine; 2% lidocaine 5 mL with 15 IU/mL hyaluronidase (curved Visitec cannula); pressure-lowering device for 5 min

D: topical 4% lignocaine 2 drops; 2% lignocaine 1 mL with 1:10,000 adrenaline (curved sub-Tenon Cannula)

E: oral 150 Kg clonidine (1 h preoperative); topical oxybuprocaine drops; 50:50 2% lidnocaine and 0.5%

bupivacaine with 25 IU/mL hyaluronidase; Honan balloon 30 mm Hg (for 15 min)

Describe control:

peribulbar anaesthesia

A: topical 1% amethocaine; 1-injection technique

50:50 2% lidnocaine and 0.5% bupivacaine 4-5 mL

(sharp 5-in peribulbar needle); Honan balloon for 7 min

B: topical 0.4% benoxinate; 1-injection technique

0.5% bupivacaine 4 mL (25-gauge sharp needle)

C: topical 0.5% proxymetacaine and 1% tetracaine; subconjunctival 0.1% lidocaine 1 mL (30-gauge, 10-mm needle);

2-injection technique 2% lidocaine with 1:200,000 adrenaline and 15 IU/mL hyaluronidase (25-gauge, 25-mm Quinke point needle); pressure-lowering device for 5 min

D: topical 4% lignocaine 2 drops; 2-injection technique 2% lignocaine 5 mL with 1:10,000 adrenaline

(24-gauge needle)

E: oral 150 Kg clonidine (1 h preoperative); topical

oxybuprocaine drops; 1-injection technique 50:50 2% lidnocaine and 0.5% bupivacaine with 25 IU/mL hyaluronidase (25-gauge needle); Honan balloon 30 mm Hg (for 15 min)

End-point of follow-up:

A: not reported; duration 6 months

B: not reported; duration 4 months

C: not reported; duration not reported

D: not reported; duration 9 months

E: not reported; duration not reported

For how many participants were no complete outcome data available?

(intervention/control)

“Follow-up of patients in these studies was complete and sufficient for all outcome measures, with the exception of postoperative pain, which may have required a longer follow-up period.”

Pain during anaesthesia administration

Median on 10- point visual analogue score measured postoperatively

C: 0 vs. 0, p=0.75

Mean on 5-point visual analogue score

D: 0.26 vs. 0.82, p<0.05

Some pain reported

C: 11/50 vs. 12/50, RR=0.92 [95% CI 0.45, 1.88]

Intraoperative pain

Median on 10- point visual analogue score measured postoperatively

C: 0 vs. 0

Mean on 5-point visual analogue score

D: 0.07 vs. 0.15, p=?

7-Point visual analog score measured postoperatively

A: ? vs. ?, p>0.05

4-Point visual analog score

B: ? vs. ?, p=0.673

Some intra operative pain reported

C: 0/50 vs. 1/50, RR= 0.33 [95% CI 0.01, 7.99]

Postoperative pain

5-Point visual analogue score measured at 4 h postoperative

D: ? vs. ?, p>0.05

Mean on 4-Point visual analogue score measured at 24 h postoperative

B: 0.53 vs. 0.13, p=0.007, favouring peribulbar anaesthesia

Globe and lid akinesia

Globe movement

A: (4 point VAS): p<0.005, favouring sub-Tenon’s anaesthesia

B: (scale 0-12): ? vs. ?, p>0.05

C: (median on scale 0-8): 0 vs. 0, p=0.88

D: (mode on scale 0-12) 10 vs. 0, p<0.05; 72/80≥ 6 vs. 85/88≤4

E: p=0.0001 favouring sub-Tenon’s anaesthesia

Complications of anesthesia

Chemosis

C: 29/50 vs. 33/50, p=0.4, RR= 0.88 [95% CI 0.65, 1.20]

D: ? vs. ? , p>0.05

Subconjunctival haemorrhage

C: 25/50 vs. 1/50, p<0.001, RR= 25.00 [95% CI 3.52, 177.48]

D: ? vs. ? , p>0.05

Brief description of author’s conclusion:

“A systematic search of the literature revealed that there is a paucity of robust evidence comparing sub-Tenon and peribulbar anesthesia. Based on the best available evidence, there is no significant difference in the efficacy of peribulbar compared with sub-Tenon anesthesia for cataract surgery; however, the potential complications of peribulbar anesthesia are more serious.”

Methodological quality of SR was good, except there was no reporting of publication bias and conflict of interest was not reported for the included RCT’s .

Methodological quality of included RCT’s : adequate randomization (including concealment of allocation) and blinding (patients/personnel, outcome measurement) in one RCT (E); possible inadequate randomization in one RCT (A) and unclear randomization procedure in other RCT’s (B, C and D). No information on blinding in two RCT’s (A, D), blinding of participants and/or personnel in two RCT’s (B, C) and blinding of outcome assessment in one RCT (B).

Results were not pooled because of clinical heterogeneity: different anaesthetic types were

used in each study, and each varied in their combinations,

volumes, and concentrations, no consistency in number of anaesthetists and surgeons involved.

There was also heterogeneity in the reporting of outcome measures among the

included studies.

Zhao, 2012

[individual study characteristics deduced from Zhao, 2012]

PS., study characteristics and results are extracted from the SR (unless stated otherwise)

SR and meta-analysis of RCT’s

Literature search up to July 2010

A: Chan, 2002

B: Chung, 2004

C: Gombos, 2007

D: Jacobi, 2000

E: Nielsen, 1998

F: Patel, 1996

G: Patel, 1998

H: Rengaraj, 2004

I: Roman, 1996

J: Ryu, 2009

K: Sauder, 2003

L: Strobel, 1996

M: Uusitalo, 1999

N: Virtanen, 1998

O: Zehetmayer, 1996

Study design: RCT not reported whether parallel or cross-over design

Setting and Country:

A: China

B: China

C: Hungary

D: Germany

E: Denmark

F: USA

G: USA

H: India

I: France

J: Korea

K: Germany

L: Germany

M: Finland

N: Finland

O: Austria

SR authors affiliated to Department of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

Source of funding:

Grants from the Shanghai Leading

Academic Discipline Project (Project No. S30205) and General Program of

the Biomedical Division of the Shanghai Science and Technology Commission

(Project No. 10411966200).

Inclusion criteria SR: RCT, the patients included

presented with cataract and were older than 18 years of age, the study intervention included topical anaesthesia and retrobulbar/peribulbar anaesthesia, and the study

assessed at least 1 of the defined primary and secondary objectives

Exclusion criteria SR: topical anaesthesia in combination with other techniques, such as intracameral lidocaine, regional nerve block, and sponge soaked with drugs inserted deeply into the

conjunctival fornices.

15 studies included

Important patient characteristics at baseline:

Number of eyes: 2205

(1084 topical vs. 1121 retrobulbar /peribulbar)

N, mean age(±SD or (range))

Topical vs. control group (retrobulbar or peribulbar)

A: n=49 vs. n=58, 73.6 (46–90) vs. 73.8 (50–88) yrs

B: n=35 vs. n=41, 70.2±10.8 vs. 75.0±7.8 yrs

C: n=58 vs. n=57, 74±10 vs. 72±10 yrs

D: n=238 vs. n=238, 73.1±5.6 vs. 72.1±6.8 yrs

E: n=44 vs. n=44, 79 (53–93) vs. 77 (59–91) yrs

F: n=69 vs. n=69, (45–85 yrs) vs. (45–85 yrs)

G: n=45 vs. n=45, (45–80 yrs) vs. (45–80 yrs)

H:n=155 vs. n=151, 57.4±8.5 vs. 57.2±8.0

I: total n=45, 73 yrs

J: n=27 vs. n=27, 65.6±7.9 vs. 65.5±7.9

K: n=71 vs. n=69, 73.2±1.4 vs. 74.1±1.9

L: n=27 vs. n=27, 71.3 (52–87) vs. 68.5 (26–86) yrs

M: n=136 vs. n=163, 72.2 (33–89) vs. 71.3 (30–93) yrs

N: n=49 vs. n=51, 67.3 (24–80) vs. 66.6 (37–80)

O: total: n=36, ? yrs

Sex (M/F):

Topical vs. control group (retrobulbar or peribulbar)

A: 22/27 vs. 28/30

B: 11/24 vs. 22/19

C: 20/38 vs. 20/37

D: 88/150 vs. 84/154

E: 21/23 vs. 15/29

F: not reported

G: not reported

H: 97/57 vs. 76/74

I: total: 17/28

J: 11/16 vs. 11/16

K: not reported

L: 15/12 vs. 18/9

M: not reported

N: 15/34 vs. 16/35

O: not reported

Groups comparable at baseline?

Based on age and sex as reported for study groups of most RCT’s , groups seem comparable at baseline.

Describe intervention:

topical anaesthesia

A: 2% lidocaine

B: 2% lidocaine

C: 2% oxybuprocaine

D 2% lidocaine

E: 4% lidocaine

F: 0.75% bupivacaine

G: 0.75% bupivacaine

H: 0.5% proparacaine

I: 1% tetracaine

J: 2% lidocaine

K: 0.4% oxybuprocaine

L: 4% cocaine

M: 0.75% bupivacaine

N: 0.4% oxybuprocaine

O: 4% lidocaine

Describe control:

regional anaesthesia: retrobulbar or peribulbar anaesthesia

Retrobulbar

A: 2% lignocaine, 0.5% bupivacaine hyaluronidase

C: 2% lidocaine, 0.5% bupivacaine

D: 2% lidocaine, 0.5% bupivacaine hyaluronidase

F: 2% lidocaine, 0.75% bupivacaine hyaluronidase

G: 2% lidocaine, 0.75% bupivacaine hyaluronidase

H: 2% lidocaine adrenaline

hyaluronidase

J: 2% lidocaine hyaluronidase

Peribulbar

I: 2% lidocaine, 0.5% bupivacaine

K: 2% mepivacaine, hyaluronidase

L: 2% lidocaine, 0.5% bupivacaine

M: 2% lidocaine, 0.75% bupivacaine hyaluronidase

N: 2% lidocaine, 0.5% bupivacaine hyaluronidase

O: 2% lidocaine, 0.5% bupivacaine hyaluronidase

Retrobulbar/peribulbar

B: 2% lignocaine

E: 2% lidocaine, 0.5% bupivacaine hyaluronidase

End-point of follow-up:

Not reported per included RCT

For how many participants were no complete outcome data available?

(intervention vs. control)

A: complete outcome data

B: complete outcome data

C: complete outcome data

D: complete outcome data

E: 1/44 vs. 1/44

F: complete outcome data

G: complete outcome data

H: 1/155 vs. 1/151

I: complete outcome data

J: complete outcome data

K: complete outcome data

L: complete outcome data

M: complete outcome data

N: complete outcome data

O: complete outcome data

Topical anaesthesia vs. retrobulbar anaesthesia

Intraoperative pain

Pain during surgery rated on a visual analogue scale.

Standardized mean difference [95% CI]:

D: 0.08 [-0.10, 0.26]

F: 0.19 [-0.15, 0.52]

G: 0.55 [0.12, 0.97]

J: 2.10 [1.42, 2.77]

Pooled effect (random effects model) 0.65 [95% CI 0.05 to 1.24] favoring retrobulbar anesthesia

Heterogeneity (I²): 91.3%

Postoperative pain

Pain after surgery (time point nog reported) rated on a visual analogue scale

Standardized mean difference [95% CI]:

F: 0.44 [0.10, 0.78]

G: 0.33 [-0.08, 0.75]

J: 1.85 [1.21, 2.50]

Pooled effect (random effects model) 0.83 [95% CI 0.07 to 1.58] favoring retrobulbar anesthesia.

Heterogeneity (I²): 88.2%

Intraoperative difficulties

assessed by surgeons, continuous scale with ideal

cooperation defined as 0

Standardized mean difference [95% CI]:

D: 0.12 [-0.06, 0.30]

F: -0.13 [-0.46, 0.21]

G: 0.70 [0.27, 1.13]

Pooled effect (random effects model) 0.20 [95% CI -0.17 to 0.58]

Heterogeneity (I²): 78.1%

Topical anaesthesia vs. peribulbar anaesthesia

Intraoperative pain

Pain during surgery rated on a visual analogue scale.

Standardized mean difference [95% CI]:

K: 0.03 [-0.30, 0.36]

M: 0.62 [0.39, 0,86]

N: 1.31 [0.88, 1.74]

O: -0.02 [-0.48, 0.45]

Pooled effect (random effects model) 0.49 [95% CI -0.04 to 1.01]

Heterogeneity (I²): 88.9%

Postoperative pain

Pain after surgery (time point not reported) rated on a visual analogue scale

Standardized mean difference [95% CI]:

M: 0.37 [0.14, 0.60]

Intraoperative difficulties

assessed by surgeons, continuous scale with ideal

cooperation defined as 0

Standardized mean difference [95% CI]:

K: 0.22 [-0.11, 0.55]

M: 0.82 [0.59, 1.06]

O: -0.39 [-0.86, 0.08]

Pooled effect (random effects model) 0.24 [95% CI -0.43 to 0.91]

Heterogeneity (I²): 91.6%

Topical anaesthesia vs. regional (retrobulbar/peribulbar) anaesthesia

Intraoperative pain

Pain during surgery rated on a visual analogue scale.

D, F, G, J, K, M, N, O (see above)

Pooled standardized mean difference (random effects model) 0.55 [95% CI 0.19 to 0.91] favoring regional anesthesia

Heterogeneity (I²): 89.5%

Pain during surgery as dichotomous outcome

C, I, E (no individual study data reported):

51/147 vs. 15/146, rate difference=4.55, (95% CI: 2.58 to 8.05), p<0.00001

Postoperative pain

Pain after surgery (time point not reported) rated on a visual analogue scale

F, G, J, M (see above)

Pooled standardized mean difference (random effects model) 0.67 [95% CI 0.20 to 1.13] favoring regional anesthesia

Heterogeneity (I²): 84.0%

Pain after surgery as dichotomous outcome

C, I (no individual study data reported):

38/103 vs. 16/102, rate difference=3.41 (95% CI: 1.76 to 6.60), p=0.0003

Intraoperative difficulties

assessed by surgeons, continuous scale with ideal

cooperation defined as 0

Standardized mean difference [95% CI]:

D, F, G, K, M, O (see above)

Pooled standardized mean difference (random effects model) 0.24 [95% CI -0.11 to 0.59]

Heterogeneity (I²): 87.7%

Inadvertent eye movement

E, F, G, L, N (no individual study data reported):

94/234 vs. 28/196, rate difference=3.91 (95% CI: 2.54 to 6.03), p<0.00001

Need for additional anaesthesia during surgery

A, D, F, G, I, K, M, O (no individual study data reported):

9/689 vs. 2/723, rate difference= 3.88 (95% CI 1.18 to 12.75), p=0.03

Preference of anaesthesia

(in patients operated on both eyes with different anaesthesia techniques)

E, F, I, M O (no individual study data reported):

69/133 vs. 33/133, rate difference= 3.11 (95% CI 1.90 to 5.09), p<0.00001

Anaesthesia-related complications

Chemosis

D, E, F, G, K, M (no individual study data reported):

1/603 vs. 72/628, rate difference= 0.08 (95% CI 0.0 to 0.13)p<0.00001

Periorbital hematoma

D, E, F, G, I, K, L, M, O (no individual study data reported):

0/667 vs. 51/692, rate difference =0.10 (95% CI 0.05 to 0.18), p<0.00001

Subconjunctival hemorrhage

D, E, F, G, K, M (no individual study data reported):

1/603 vs. 26/628, rate difference=0.14 (95% CI 0.07 to 0.31), p<0.00001

Postoperative nausea and vomiting

A, J (no individual study data reported):

3/76 vs. 1/85, rate difference=3.36 (95% CI 0.46 to 24.68), p=0.23

Postoperative analgesics

J, O (no individual study data reported):

9/63 vs. 4/63, rate difference=2.39 (95% CI 0.75 to 7.61), p=0.14

Intraoperative complications

Capsular rupture

A, C, D, E, F, G, H, I, K, L, M, N, O (no individual study data reported):

18/1022 vs. 20/1053, rate difference=0.94 (95% CI 0.50 to 1.79), p=0.86

Zonular tear

D, E, L, N (no individual study data reported):

12/358 vs. 7/360, rate difference=1.72 (95% CI 0.69 to 4.30), p=0.24

Iris prolapse

D, E, F, K, N (no individual study data reported):

5/471 vs. 1/471, rate difference=3.83 (95% CI 0.77 to 19.08), p=0.10

Systemic complications

“No major systemic complications, such as respiratory depression,

oxygen desaturation, or cardiopulmonary arrest, were reported in any of the trials.”

Postoperative visual acuity

C, M, L: “Within the scope of the 3 studies, preoperative visual acuity showed no significant difference between the 2 groups.”

Brief description of author’s conclusion:

“Compared with regional anesthesia, topical anesthesia does not provide the same excellent pain relief in cataract

surgery; however, it achieves similar surgical outcomes. Topical anesthesia reduces injection-related complications and alleviates patients’ fear of injection. The choice of TA is not suitable for patients with a higher initial

blood pressure or greater pain perception.”

It was not clear how the authors came to the rate difference. The numbers reported in this evidence table were extracted from table 2. From the original publication.

Methodological quality of SR: excluded RCTs were not described, risk of publication bias was not assessed and conflict of interest was not reported for the included RCTs.

Methodological quality of included RCTs: although the authors state that the Cochrane Risk of Bias Tool is used for assessing methodological quality of included RCTs, they present a Jadad score for each RCT. All included RCTs have a Jadad score of 3 or higher. One of the RCTs (M) has a score of 6, however usually a score of 5 is the highest possible score.

Although it seems all included RCTs are of reasonable to good methodological quality, the exact assessment by review authors remains unclear. I

was not

It as

It

Results should be interpreted with caution as there was heterogeneity in clinical aspects (interventions, pain score measurements) and definitions used in the included studies.

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Buys,

1993

Type of study:

RCT

Setting: single center

Country: Canada

Source of funding: not reported

Inclusion criteria:

Patients undergoing either day-surgery or inpatient trabeculectomies.

Exclusion criteria:

not reported

N total at baseline:

Intervention: 22

Control: 17

Important prognostic factors²:

Mean age (yrs):

I: 63.5

C: 63.4

Sex:

I: 50% M

C: 29% M

Groups comparable at baseline? Relatively more female patients in the retrobulbar anesthesia group.

Sub-Tenon’s anesthesia

Before surgery topical 0.5% tetracaine was instilled in both eyes.

Sub-Tenon’s anesthesia consisted of 2% lidocaine without epinephrine injected over the superior, medial and lateral recti muscles.

Patients received a van Lint lid block and a standardized sedative.

Retrobulbar anesthesia

Before surgery topical 0.5% tetracaine was instilled in both eyes.

Retrobulbar anesthesia consisted of a 1.5 ml injection of a 1:1 mixture of 2% lidocaine without epinephrine and 0.5% plain bupivacaine with hyaluronidase.

Patients received a van Lint lid block and a standardized sedative.

Length of follow-up:

24 hours

Loss-to-follow-up:

no losses to follow-up described

Incomplete outcome data:

no information on incomplete outcome data provided

Sub-Tenon’s anesthesia vs. retrobulbar anesthesia

Presence of eye movements

3/22 (14%) vs. 0/16, p=NS

Surgical exposure

poor: 1/22 (5%) vs. 0, p=NS

Intraoperative complications

2/22 (9%) vs. 3/17 (18%), p=NS

(complications monitored included retrobulbar hemorrhage, globe perforation, retinal vascular occlusion, subconjunctival hermorrhage, brains stem anesthesia, optic nerve trauma)

Mean intraoperative discomfort (5-point scale: 1 is least and 5 is most discomfort)

1.7 vs. 1.6, p=NS; (95% CI -0.6 to 0.4)

Need for supplemental anesthesia

2/22 (9%) vs. 10/17 (60%), p<0.002; (95% CI 0.2 to 0.8)

Postoperative complications

0/22 v. 1/17 (6%), p=NS

(complications specifically surveyed were bleb leak and ptosis)

Mean discomfort 24 hours postoperative (5-point scale: 1 is least and 5 is most discomfort)

1.6 vs. 2.2, p=NS(95% CI -0.8 to 0.6)

Postoperative analgesia use

7/22 (32%) vs. 12/17 (71%), p<0.03;

RR=0.45 (95% CI 0.23 to 0.89)

Risk of performance bias and detection bias. No information on allocation concealment. Other items (outcome reporting, completeness of follow-up): low risk of bias.

Dole, 2014

Type of study: RCT

Setting: single center

Country: India

Source of funding: none

Inclusion criteria:

40 to 75 years old, uncomplicated senile cataracts, without a history of previous ocular co-morbidities, injury, or surgery.

Exclusion criteria:

allergy to paracaine, history of convulsion/epilepsy, presence of other ocular co-morbidities such as exfoliation syndrome, uveitis, myopia with axial length >26 mm, hyperopia with axial length < 21 mm, posterior synaechia, phacodonesis, were

hearing impaired, had dementia, strabismus or poor fixation due to nystagmus.

N total at baseline:

Intervention: 500

Control: 500

Important prognostic factors²:

age ± SD (years):

I: 60 ±6.2

C: 59.5 ± 6.6

Sex:

I: 54.6% M

C: 50.2% M

Type of cataract

I vs. C:

• NS₂grade 2

8% vs. 7.8%

• NS₂+cortical

 40.4% vs. 42.6%

• NS₃

38% vs. 38%

• NS₃+cortical
  12.8% vs. 9.6%
• Sub-capsular

0.8% vs. 1.6%

Preoperative vision

I vs. C:

• <20/400

0.8% vs. 1.0%

• <20/200 - 20/400

13.4% vs. 16.8%

• 20/60 - 20/200

54% vs. 54%

• 20/20 – 20/40

28.2% vs. 28.2%

Groups comparable at baseline?

Yes

“There were no statistically significant differences in the patient profile between groups.”

Topical anesthesia

One drop of proparacaine hydrochloride 0.5% was instilled 6 times with an interval of 5 min. Topical anesthetic was instilled soon after dilating the pupil but before the start of the surgery. Anesthesia was instilled by an assistant surgeon preoperatively.

Patients were instructed to keep their eyes closed after instillation of topical anesthetic.

A 2.8 mm sized incision in the clear cornea was created for the phaco port, and two side ports were created of 0.8 mm each. Methylcellulose was inserted in the anterior chamber, and an anterior capsulorhexsis was performed with a cystotome. To separate the cortex from the capsule, hydro-dissection and hydrodelineation were performed. Minimum energy was used for the phacoemulsification procedure.

Peribulbar anesthesia

4 ml of 2% lignocaine with 1:10000 adrenaline was injected using a 24G needle. The needle was inserted at the junction of middle and outer third of the lower orbital margin and directed toward the floor of the orbit. The eyelids were closed, and pressure was applied on the eye for 5 min. Anesthesia was administered by an anesthetist/ophthalmologist.

A 2.8 mm sized incision in the clear cornea was created for the phaco port, and two side ports were created of 0.8 mm each. Methylcellulose was inserted in the anterior chamber, and an anterior capsulorhexsis was performed with a cystotome. To separate the cortex from the capsule, hydro-dissection and hydrodelineation were performed. Minimum energy was used for the phacoemulsification procedure.

Length of follow-up:

24 hours (pain, complications, satisfaction); 4-6 weeks (visual acuity)

Loss-to-follow-up:

no losses to follow-up described.

Incomplete outcome data:

no information on incomplete outcome data provided.

Topcal anesthesia (TA) vs. peribulbar anesthesia (PA)

Pain during delivery of anesthesia

0 vs.444/500 (89%)

Patient satisfaction for anesthesia (intraoperative pain)

• Mild discomfort: 411/500 (82.2%) vs. 484/500 (96.8%)
• Moderate pain: 72/500 (14.4%) vs. 15/500 (3%)
• Not tolerable: 17/500 (3.4%) vs. 1/500 (0.002%)

More pain in the TA group

intraoperatively , p=0.003

“Satisfaction with the mitigation of pain was statistically significantly greater in the PA group compared to the TA group (χ = 10.9, df = 3, P = 0.001).

Anesthesia-related complications

“There were more anesthesia-related complications in

the PA group compared to the TA group.”

Surgeon satisfaction (level of anesthesia)

not satisfactory: 46/500 (9.2%) vs. 23/500 (4.6%),

OR 2.1 (95% CI: 1.3 to 3.5)

RR: 2.0 (95% CI: 1.23 to 3.25)

“Surgeons were more satisfied with PA compared to TA (RR = 1.4, 95% CI: 1.34–1.63).”

Adverse events or complications during surgery

1/500 (posterior capsular tear) vs. 0

Pain during 24h post-surgery

• No pain: 408/500 (81.8%) vs. 345/500 (69.1%)
• Mild discomfort: 6/500 (1.2%) vs. 10/500 (2%)
• Occasional pain: 85/500 (17%) vs. 144/500 (28.9%)

RR postoperative pain: 0.59 (95% CI 0.47 to 0.74)

Signs of inflammation at 24h post-surgery

372/500 (74.4%) vs. 310/500 (62%)

RR=1.20 (95% CI: 1.10 to 1.31)

Complications during 24h post-surgery

“significantly greater in the TA group (RR = 1.36, 95% CI: 1.17 to 1.58).”

Visual acuity (4-6 weeks postoperative)

no statistically significant differences between groups, p=0.14

Risk of performance bias and detection bias, unclear risk of reporting bias. Other items (allocation concealment and completeness of follow-up): low risk of bias.

Pablo, 2003

Type of study: RCT

Setting: Single center.

Country: Spain

Source of funding: no information

Inclusion criteria:

primary open-angle glaucoma, pseudoexfoliative

glaucoma, pigmentary glaucoma or primary closure glaucoma; confirmed with significant glaucomatous

damage of the optic nerve with visual

field defects; insufficient control of intraocular pressure (IOP) for reasons such as allergies, side-effects, poor compliance or more than two antiglaucoma

medications

Exclusion criteria:

previous surgery involving conjunctiva in the

studied eye, patient rejection and inability to follow instructions.

N total at baseline:

Intervention: 50

Control: 50

Important prognostic factors²:

age ± SD (years):

I: 72.9 ± 8.09

C: 74.02 ± 4.4

Sex:

I: 48% M

C: 44% M

Type of glaucoma

• Primary open angle

I: 38

C: 40

• Pseudoexfoliative

I: 8

C: 7

• Primary angle closure

I: 3

C: 1

• Pigmentary

I: 1

C: 2

Groups comparable at baseline?

Yes

Contact anesthesia

After instilling drops of topical lidocaine hydrochloride 2% in the eye which was to undergo surgery, a 50x15x0.5mm

absorbable gelatin sponge (Spongostan^TM; FerrosanA/S, Soeborg, Denmark) film thoroughly soaked in lidocaine hydrochloride 2% was introduced under the upper eyelid with the help of toothed forceps. After 5min the film was removed and some drops of antibiotic

were instilled. The eye was then ready for the surgical procedure.

After conjunctival limbal-based dissection, a diathermy coagulation of vessels and scleral flap was performed. The procedure was completed with a trabecular excision and scleral and conjunctival

sutures. If required, the eye globe was maintained in an adequate position by grasping the remains of the limbal conjunctival tissue with fine-toothed forceps.

Peribulbar anesthesia

Peribulbar injections of bupivacaine hydrochloride 0.75% mixed with lidocaine

2% (50 : 50 mixture) were administered

with a 25-gauge needle, giving 3ml in each of the super-temporal and infra-temporal quadrants. This was followed by 10 min of Honan balloon, after which a standard Cairns trabeculectomy was performed.

After conjunctival limbal-based dissection, a diathermy coagulation of vessels and scleral flap was performed. The procedure was completed with a trabecular excision and scleral and conjunctival

sutures. If required, the eye globe was maintained in an adequate position by grasping the remains of the limbal conjunctival tissue with fine-toothed forceps.

Length of follow-up:

24 hours (pain)

1 month (complications)

Loss-to-follow-up:

no losses to follow-up described.

Incomplete outcome data:

no information on incomplete outcome data provided.

Contact anesthesia vs. peribulbar anesthesia

Pain during delivery of anesthesia (5-point scale: 0= no pain, 4=severe pain)

(mean ± SD)

0.12 ± 0.32 vs. 2.46 ± 0.12, p<0.001

Mean difference: -2.34, 95% CI -2.43 to -2.25

Pain during surgery (5-point scale: 0= no pain, 4=severe pain) (mean ± SD)

0.38 ± 0.6 vs. 0.58±0.1, p=0.127

Mean difference: -0.20, 95% CI -0.37 to -0.03

Pain 30 minutes postoperatively (5-point scale: 0= no pain, 4=severe pain)

(mean ± SD)

0.26 ± 0.49 vs. 0.22 ± 0.46, p=0.639

Mean difference: 0.04, 95% CI -0.15 to 0.23

Pain 24 hours postoperatively

2/50 vs. 3/50,

Risk ratio: 0.67, 95% CI 0.12 to 3.82

Surgical parameters

• BP increase over 20/10

1/50 vs. 1/50, p=1

• Pulse rate increase >20bpm

1/50 vs. 2/50, p=0.558

• IV sedation required

2/50 vs. 2/50, p=1

• Subjective surgical stress (scale 0-4) (mean ± SD)

0.18 ± 0.44 vs. 0.12 ± 0.39, p=0.385

Postoperative parameters: complications

• Chemosis/conjunctival haemorrhage

0/50 vs. 6/50, p=0.012

• Hyphema

4/50 vs. 3/50, p=0.695

• Leaking bleb

3/50 vs. 1/50, p=0.307

• Shallow anterior chamber

2/50 vs. 3/50, p=0.646

• Choroidal detachment

1/50 vs. 2/50, p=0.558

• Complications requiring reoperation

1/50 vs. 2/50, p=0.558

“there were no operative

complications in either group”

Risk of performance bias and detection bias. No information on allocation concealment. Other items (outcome reporting, completeness of follow-up): low risk of bias.

Pham 1996

Type of study: RCT

Setting: single center

Country: Germany

Source of funding: no information

Inclusion criteria:

planned cataract surgery

Exclusion criteria:

deafness, disorientated or scared patients, patients having chronic obstructive pulmonary disease. Previous surgery on eye to be operated, pupil size <3 mm

N total at baseline:

Group A: 50

Group B: 50

Group C: 50

Important prognostic factors²:

age ± SD (years):

A: 71.8 ±9.6

B: 71.7 ± 13.7

C: 72.4 ± 10.7

Sex:

A: 32% M

B: 22% M

C: 28% M

Groups comparable at baseline?

Differences between groups regarding sex.

A: oxybuprocaine

sponge anesthesia

20 minutes preoperatively: instillation of one or two drops oxybuprocain, sponge soaked in oxybuprocain placed on conjunctiva

Oculopression 40mm Hg

for 15 minutes. tropicamide, epinephrine and scopolamine were used to enlarge the pupil.

If necessary, for light sedation midazolam 1-1.5 mg IV was given. Directly postoperative peripheral acting pain medication (e.g. paracetamol) was provided.

B: oxybuprocaine sponge

anesthesia combined with mild systemic analgesia (tramadol p.o.).

Premedication with 0.5 to 1.0 mg/kg bodyweight tramadol p.o. 30 minutes preoperatively.

20 minutes preoperatively: instillation of one or two drops oxybuprocain, sponge soaked in oxybuprocain placed on conjunctiva

Oculopression 40mm Hg

for 15 minutes. tropicamide, epinephrine and scopolamine were used to enlarge the pupil.

If necessary, for light sedation midazolam 1-1.5 mg IV was given. Directly postoperative peripheral acting pain medication (e.g. paracetamol) was provided.

C: retrobulbar injection (prilocaine/etidocaine mixture)

Oculopression 40mm Hg

for 15 minutes. tropicamide, epinephrine and scopolamine were used to enlarge the pupil.

If necessary, for light sedation midazolam 1-1.5 mg IV was given. Directly postoperative peripheral acting pain medication (e.g. paracetamol) was provided.

Length of follow-up:

4 to 5 hours

Loss-to-follow-up:

no losses to follow-up described.

Incomplete outcome data:

no information on incomplete outcome data provided.

Pain or discomfort during

operation

A: 14%

B: 6%

C: 6%

A vs. B: p=0.08 to 0.42

A vs. C: p<0.05

B vs. C: p=0.07 to 0.55

Intraoperative complications

“no capsular tears or vitreous losses”

Postoperative pain (scale 0-5; but dichotomously presented)

A: pain 6%, discomfort 30%

B: no difference in pain or discomfort compared to A

C: pain or discomfort 10%

A vs. C: p<0.05

Postoperative nausea

B: 6/50 (12%)

Risk of performance bias and detection bias. No information on allocation concealment. Other items (outcome reporting, completeness of follow-up): low risk of bias.

Shammas, 1997

Type of study: RCT

Setting: single center

Country: USA

Source of funding: no information

Inclusion criteria:

patients undergoing phacoemulsification

Exclusion criteria:

age < 40 years, miotic pupil

N total at baseline:

Intervention: 197

Control: 205

Important prognostic factors²:

age ± SD (years):

I: 73.7 ± 9.0

C: 71.3 ± 9.9

Sex:

I: 35.0 % M

C: 39.1% M

Groups comparable at baseline?

Yes

“There was no statistically significant difference between the two groups in age, sex, and operated eye”

Topical/subconjunctival anesthesia

This group received a few drops of Xylocaine-MPF in

the superior and inferior fornices and on the corneal

surface at two 5 minute intervals, allowing the anesthetic to bathe the cornea for a few seconds. Then, Xylocaine-MPF (0.2 to 0.3 mL) was injected under the conjunctiva at the 12 o'clock position. No ocular

massage, Honan balloon, or lid block was used. Patients

in this group were given 0.5 mg of midazolam hydrochloride (Versed®) and 0.025 mg of fentanyl citrate (Sublimaze®) intravenously.

Mean amount of Xylocaine-MPF injected locally was 0.25 ± 0.02 mL; statistically significant difference with control group (p< .001).

Retrobulbar/peribulbar anesthesia

Before the anesthetic was administered, patients in this group received an intravenous (IV) bolus of 100 to 150 mg of sodium thiopental (Pentothal®). The eye was then directed into the primary position. The inferior temporal rim was palpated. A 27 gauge, 3.5 cm long needle, inserted 5.0 to 10.0 mm from the lateral

canthus, was used to inject 2.5 mL of lidocaine 4%

(Xylocaine-MPF®) according to the method described

by Atkinson; the remaining 0.5 mL was injected in the peribulbar space as the needle was withdrawn. Xylocaine-MPF was applied topically on the cornea, and 0.2 to 0.3 mL was injected subconjunctivally at the

12 o'clock position. The eye was then gently massaged

for 10 seconds. No lid block was given.

Mean amount of Xylocaine-MPF injected locally was 3.25 mL ± 0.10 (SD); statistically significant difference with intervention group (p< .001).

Length of follow-up:

1 month

Loss-to-follow-up:

no losses to follow-up described.

Incomplete outcome data:

no information on incomplete outcome data provided.

Topical/subconjunctival anesthesia vs. Retrobulbar/peribulbar anesthesia

Pre-anesthesia

• Short period of apnea and airway obstruction

0 vs. 48/205 (23.4%)

• Continuous episodes of coughing

0 vs. 10/205 (4.9%)

p<0.001

Intraoperative complications

• Retrobulbar haemorrhage

0 vs. 2/205 (1.0%), p>0.1

• Capsular rupture

2/197 (1.0%) vs. 8/205 (3.9%), p>0.05

• With anterior capsular tear: 2/197 (1.0%) vs. 2/205(1.0%), p>0.1
• With positive vitreous pressure: 0 vs. 6/205 (2.0%), p<0.02

Postoperative pain

18/197 (9.1%) vs. 20/205 (9.8%), p>0.1

RR=0.94 (95% CI 0.51 to 1.72)

Postoperative complications

• Lid bruising

0 vs. 30/205 (14.6%), p<0.001

• Diplopia

0 vs. 2/205 (1.0%), p>0.1

• Upper lid ptosis

1/197 (0.5%) vs. 4/205 (2.0%), p>0.1

postoperative visual acuity of >20/25

at 1 day: 56/197 (28.4%) vs. 34/205 (16.7%), p<.01

at 1 week: 102/197 (51.8%) vs. 91/205 (44.8%), p>.1

at 1 month: 151/197 (76.6%) vs. 155/2015 (76.4%), p>.1

Risk of performance bias and detection bias. No information on allocation concealment. Other items (outcome reporting, completeness of follow-up): low risk of bias.

Study

First author, year

Appropriate and clearly focused question?¹

Yes/no/unclear

Comprehensive and systematic literature search?²

Yes/no/unclear

Description of included and excluded studies?³

Yes/no/unclear

Description of relevant characteristics of included studies?⁴

Yes/no/unclear

Appropriate adjustment for potential confounders in observational studies?⁵

Yes/no/unclear/notapplicable

Assessment of scientific quality of included studies?⁶

Yes/no/unclear

Enough similarities between studies to make combining them reasonable?⁷

Yes/no/unclear

Potential risk of publication bias taken into account?⁸

Yes/no/unclear

Potential conflicts of interest reported?⁹

Yes/no/unclear

Alhassan, 2015

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

No

No (only for systematic review, not for included studies)

Guay, 2015

Yes

Yes

Yes

Yes

Not applicable

Yes

Yes

Yes

No (only for systematic review, not for included studies)

Page, 2009

Yes

No

(search period unknown, only Medline was searched)

No

(no description of excluded studies)

Yes

Unclear

(not mentioned)

Yes, for RCT’s , not mentioned for observational studies

Yes

No

No (only for systematic review, not for included studies)

Wang, 2012

Yes

Yes

Yes

Yes

Not applicable

Yes, however results were only partly reported

Yes

No

No (only for systematic review, not for included studies)

Zhao, 2012

Yes

Yes

No

(no description of excluded studies)

Yes

Not applicable

Yes

Yes

No

No (only for systematic review, not for included studies)

Study reference

(first author, publication year)

Describe method of randomisation¹

Bias due to inadequate concealment of allocation?²

(unlikely/likely/unclear)

Bias due to inadequate blinding of participants to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of care providers to treatment allocation?³

(unlikely/likely/unclear)

Bias due to inadequate blinding of outcome assessors to treatment allocation?³

(unlikely/likely/unclear)

Bias due to selective outcome reporting on basis of the results?⁴

(unlikely/likely/unclear)

Bias due to loss to follow-up?⁵

(unlikely/likely/unclear)

Bias due to violation of

intention to treat analysis?⁶

(unlikely/likely/unclear)

Buys, 1993

No information on method of randomisation.

unclear

no information on allocation concealment

unclear

Although “patients were unaware as to which type of local anesthetic they received.”, procedures are different.

likely

Blinding to treatment allocation not possible.

likely

Subjective outcome measures, reported by surgeons who are not blinded to treatment allocation are susceptible to bias.

unlikely

No protocol available, however, results are reported for all outcomes listed in methods.

unlikely

No loss to follow-up mentioned.

unlikely

Number of patients randomized seemed to be analyzed in each group.

Dole, 2014

“The randomization schedule for each surgeon was generated by an epi-table for 1000 surgeries.”

unlikely

“Patients were randomly assigned to a group using the sealed envelope method after the patient was in the preanesthesia room.”

likely

Blinding to treatment allocation not possible.

“The patients and the surgeon did not know the group assignment until 10 min preoperatively.”

likely

Blinding to treatment allocation not possible.

“The patients and the surgeon did not know the group assignment until 10 min preoperatively.”

likely

Subjective outcome measures, most of them self-reported by patients and/or surgeons, who are not blinded to treatment allocation.

unclear

No protocol available, results for complications reported, however not clear described in methods what complications were assessed. Outcomes presented in abstract seem the same outcomes as presented in main text, however results differ.

unlikely

No loss to follow-up; 500 participants randomized to each group and 500 participants analysed in each group.

unlikely

500 participants randomized to each group and 500 participants analysed in each group.

Pablo, 2003

“Randomization was made prospectively using computer-

generated randomization charts”

unclear

no information on allocation concealment

likely

Blinding to treatment allocation not possible.

likely

Blinding to treatment allocation not possible.

likely

Outcomes assessed by either patient or care providers, who aren’t blinded to treatment allocation.

unlikely

No protocol available, however, results are reported for all outcomes listed in methods.

unlikely

No loss to follow-up;

50 participants randomized to each group and 50 participants analysed in each group.

unlikely

50 participants randomized to each group and 50 participants analysed in each group.

Pham, 1996

No information on method of randomisation.

unclear

no information on method of randomisation.

likely

Blinding to treatment allocation not possible.

likely

Blinding to treatment allocation not possible.

likely

Outcomes assessed by either patient or care providers, who aren’t blinded to treatment allocation.

unlikely

No protocol available, however, results are reported for all outcomes listed in methods.

unlikely

No loss to follow-up;

50 participants randomized to each group and 50 participants analysed in each group.

unlikely

50 participants randomized to each group and 50 participants analysed in each group.

Shammas, 1997

No information on method of randomisation.

unclear

no information on method of randomisation.

likely

Blinding to treatment allocation not possible.

likely

Blinding to treatment allocation not possible.

likely

Outcomes assessed by either patient or care providers, who aren’t blinded to treatment allocation.

unlikely

No protocol available, however, results are reported for all outcomes listed in methods.

unlikely

No loss to follow-up; number of patients randomized were analyzed in each group.

unlikely

Number of patients randomized were analyzed in each group.