Prophylactic non‐steroidal anti‐inflammatory drugs for the prevention of macular oedema after cataract surgery

Blanche X Lim<sup>a</sup>; Chris HL Lim<sup>a</sup>; Dawn K Lim<sup>a</sup>; Jennifer R Evans; Catey Bunce; Richard Wormald

doi:10.1002/14651858.CD006683.pub3

Scolaris Content Display Scolaris Content Display

Contenido relacionado

Ir a:

Revisiones y protocolos relacionados
Respuestas clínicas Cochrane
Guías
Temas

Revisiones y protocolos relacionados

Respuestas clínicas Cochrane

Topics

Temas

Figure 1

Study flow diagram.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Funnel plot of comparison: 1 NSAIDs plus steroids versus steroids, outcome: 1.4 Macular oedema.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Funnel plot of comparison: 2 NSAIDs versus steroids, outcome: 2.2 Macular oedema.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 1 Poor vision due to MO.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 2 Central retinal thickness.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.3

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 3 Total macular volume.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.4

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 4 Macular oedema.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.5

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 5 Inflammation.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.6

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 6 Inflammation (flare).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.7

Comparison 1 NSAIDs plus steroids versus steroids, Outcome 7 BCVA.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 NSAIDs versus steroids, Outcome 1 Central retinal thickness.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 NSAIDs versus steroids, Outcome 2 Macular oedema.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.3

Comparison 2 NSAIDs versus steroids, Outcome 3 Inflammation (flare).

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.4

Comparison 2 NSAIDs versus steroids, Outcome 4 BCVA.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. NSAIDS plus steroids compared with steroids for the prevention of macular oedema after cataract surgery

NSAIDs plus steroids compared with steroids for the prevention of macular oedema after cataract surgery
Patient or population: people having cataract surgery Setting: eye hospital Intervention: NSAIDs plus steroids Comparison: steroids
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with steroids	Risk with NSAIDs plus steroids	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Poor vision due to MO at 3 months after surgery	74 per 1000	30 per 1000 (17 to 56)	RR 0.41 (0.23 to 0.76)	1360 (5 RCTs)	⊕⊕⊝⊝ LOW ^{1 2}	‐
Poor vision due to MO at 12 months after surgery	20 per 1000	26 per 1000 (2 to 407)	RR 1.32 (0.09 to 20.37)	88 (1 RCT)	⊕⊝⊝⊝ VERY LOW ^{1 3}	‐
Quality of life at 3 months after surgery	See comment	‐	‐	74 (1 RCT)	‐	Reported in 1 study only using COMTOL questionnaire. Data not fully reported but no significant differences in terms of quality of life, compliance and satisfaction scores.
Central retinal thickness at 3 months after surgery; assessed with OCT	See comment	‐	‐	1021 (8 RCTs)	‐	Trial results were inconsistent (I² = 87%). Results ranged from ‐30.9 microns in favour of NSAIDs plus steroids to +7.44 microns in favour of steroids alone.
Adverse effects	See comment	‐	‐	(18 RCTs)	‐	In general, no major adverse effects were noted. The main consistent observation was burning or stinging sensation with use of NSAID drops.
MO at 3 months after cataract surgery, clinically symptomatic, assessed with OCT	130 per 1000	52 per 1000 (42 to 64)	RR 0.40 (CI 0.32 to 0.49)	3638 (21 RCTs)	⊕⊕⊝⊝ LOW ^{1 4 5}
BCVA at 3 months after surgery; assessed with logMAR scale from: ‐1.3 to 1.3	See comment	‐	‐	1158 (10 RCTs)	‐	Trial results were inconsistent (I² = 70%), but all except one study found differences less than 0.1 logMAR, i.e. clinically indistinguishable from no difference.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BCVA: best corrected visual acuity; CI: confidence interval; MO: macular oedema; NSAID: non‐steroidal anti‐inflammatory drug; OCT: optical coherence tomography; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
¹ Downgraded 1 level for risk of bias: studies at unclear or high risk of bias. ² Downgraded 1 level for indirectness: extent of visual loss not always clearly defined. ³ Downgraded 2 levels for imprecision: Only 2 events. ⁴ Downgraded 1 level for publication bias: asymmetric funnel plot suggestive of publication bias. ⁵ We considered downgrading an additional 1 level for indirectness as the MO was not always OCT‐verified and it was not always clear if the MO was clinically symptomatic. However, we did not do so partly because the size of the effect was quite strong.

Summary of findings for the main comparison. NSAIDS plus steroids compared with steroids for the prevention of macular oedema after cataract surgery

Ir a la tabla de la revisión

Summary of findings 2. NSAIDS compared with steroids for the prevention of macular oedema after cataract surgery

NSAIDscompared with steroids for the prevention of macular oedema after cataract surgery
Patient or population: people having cataract surgery Setting: eye hospital Intervention: NSAIDs Comparison: steroids
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with steroids	Risk with NSAIDs	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Poor vision outcome due to MO at 3 months after surgery	‐	‐	‐	‐	‐	No data were available for this outcome.
Poor vision outcome due to MO at 12 months after surgery	‐	‐	‐	‐	‐	No data were available for this outcome.
Quality of life at 3 months after surgery						No data were available for this outcome.
Central retinal thickness at 3 months after surgery; assessed with OCT	The mean central retinal thickness at 3 months after surgery was 228 microns	MD 22.64 microns lower (38.86 lower to 6.43 lower)	‐	121 (2 RCTs)	⊕⊕⊝⊝ LOW ^{1 4}	‐
Adverse effects	‐	‐	‐	488 (4 RCTs)	‐	1 study had 2 unspecified complications in 142 participants, 2 studies reported that no adverse events were noted in either group, 1 study (55 people) mentioned 15 mild adverse effects but unclear if related to treatment.
MO at 3 months after cataract surgery; clinically symptomatic assessed with OCT	130 per 1000	35 per 1000 (23 to 53)	RR 0.27 (0.18 to 0.41)	520 (5 RCTs)	⊕⊕⊝⊝ LOW ^{1 2 3}
BCVA at 3 months after surgery; assessed with logMAR scale from: ‐1.3 to 1.3	See comment	‐	‐	220 (3 RCTs)	‐	Trial results were inconsistent (I² = 84%), but all studies found differences less than 0.1 logMAR, i.e. clinically indistinguishable from no difference.
*The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BCVA: best corrected visual acuity; CI: confidence interval; MD: mean difference; MO: macular oedema; NSAID: non‐steroidal anti‐inflammatory drug; OCT: optical coherence tomography; RCT: randomised controlled trial; RR: risk ratio.
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹ Downgraded 1 level for risk of bias: studies at unclear or high risk of bias. ² Downgraded 1 level for publication bias: asymmetric funnel plot suggestive of publication bias. ³ We considered downgrading 1 level for indirectness as the MO was not always OCT‐verified and not always clear if it was clinically symptomatic however we did not do so, partly because the effect was strong. ⁴ Downgraded 1 level for imprecision: confidence intervals include clinically unimportant effect. ⁵ Downgraded 1 level for inconsistency.

Summary of findings 2. NSAIDS compared with steroids for the prevention of macular oedema after cataract surgery

Ir a la tabla de la revisión

Table 1. 'Risk of bias' assessment

Domain	Risk of bias
Domain	Low	Unclear	High
Sequence generation	Computer‐generated list, random table, other method of generating random list.	Not reported how list was generated. Trial may be described as “randomised” but with no further details.	Alternate allocation, date of birth, records (these RCTs should be excluded).
Allocation concealment	Central centre (web/telephone access), sealed opaque envelopes.	Not reported how allocation administered. Trial may be described as “randomised” but with no further details.	Investigator involved in treatment allocation or treatment allocation clearly not masked.
Blinding of participants and personnel	Clearly stated that participants and personnel not aware of which treatment received.	Described as “double‐blind” with no information on who was masked.	Open‐label or no information on masking. We assume that in absence of reporting on this outcome, patients and personnel were not masked.
Blinding of outcome assessors	Clearly stated that outcome assessors were masked.	Described as “double‐blind” with no information on who was masked.	Open‐label or no information on masking. We assume that in absence of reporting on this outcome, assessors were not masked.
Incomplete outcome data	Missing data less than 20% (i.e. more than 80% follow‐up) and equal follow‐up in both groups and no obvious reason why loss to follow‐up should be related to outcome.	Follow‐up not reported or missing data > 20% (i.e. follow‐up < 80%) but follow‐up equal in both groups.	Follow‐up different in each group and/or related to outcome.
Selective outcome reporting	All outcomes in protocol and/or trial registry entry are reported.	No access to protocol or trial registry entry.	Outcomes in protocol and/or trial registry entry selectively reported.
Other sources of bias Note: we did not identify any important sources of other bias so this domain is omitted from the risk of bias tables.	No other source of bias.	Trial stopped early due to poor recruitment. Baseline imbalance, but not clear that it is important.	Trial stopped early because of outcome. Important baseline imbalance that might have an effect on the results.

Table 1. 'Risk of bias' assessment

Ir a la tabla de la revisión

Table 2. Studies

	Study	Country	Open‐label	Funding sources	Declaration of interest	Trial registration	Abstract only
1	Almeida 2008	Canada	Yes	Non‐industry	Reported; no CoI	NCT00335439	No
2	Almeida 2012	Canada	No	Non‐industry	Reported; no CoI	NCT01395069	No
3	Asano 2008	Japan	No	Not reported	Reported; no CoI	Not registered	No
4	Brown 1996	USA	No	Industry	Not reported	Not registered	No
5	Cervantes‐Coste 2009	Mexico	No	Not reported	Reported; no CoI	Not registered	No
6	Chatziralli 2011	Greece	No	Not reported	Not reported	Not registered	No
7	Donnenfeld 2006	USA	No	Industry/Non‐Industry	CoI	Not registered	No
8	Elsawy 2013	Egypt	No	Not reported	Reported; no CoI	Not registered	No
9	Endo 2010	Japan	Yes	Not reported	Reported; no CoI	Not registered	No
10	Italian Diclofenac Study Group 1997	Italy	No	Not reported	CoI	Not registered	No
11	Jung 2015	South Korea	No	Non‐industry	Reported; no CoI	Not registered	No
12	Kraff 1982	USA	No	Non‐industry	Not reported	Not registered	No
13	Li 2011	China	No	Not reported	Not reported	Not registered	No
14	Mathys 2010	USA	No	Non‐industry	Reported; no CoI	NCT00494494	No
15	Miyake 2007	Japan	No	Not reported	Reported; no CoI	Not registered	No
16	Miyake 2011	Japan	No	Not reported	CoI	Not registered	No
17	Miyanaga 2009	Japan	No	Not reported	Not reported	Not registered	No
18	Moschos 2012	Greece	No	Not reported	Reported; no CoI	Not registered	No
19	Quentin 1989	Germany	No	Not reported	Not reported	Not registered	No
20	Rossetti 1996	Italy	No	Not reported	Reported; no CoI	Not registered	No
21	Singh 2012	USA	No	Not reported	CoI	NCT00782717	No
22	Solomon 1995	Canada (8 sites) and Germany (2 sites)	No	Industry	Reported; no CoI	Not registered	No
23	Tauber 2006	USA	No	Industry	CoI	Not registered	Yes
24	Ticly 2014	Brazil	No	Not reported	Reported; no CoI	Not registered	No
25	Tunc 1999	Turkey	No	Not reported	Not reported	Not registered	No
26	Tzelikis 2015	Brazil	No	Not reported	Reported; no CoI	NCT02084576	No
27	Umer‐Bloch 1983	Switzerland	No	Not reported	Not reported	Not registered	No
28	Wang 2013	China	Yes	Non‐industry	Not reported	Not registered	No
29	Wittpenn 2008	USA	No	Industry	CoI	NCT00348244	No
30	Yannuzzi 1981	USA	No	Non‐industry	Not reported	Not registered	No
31	Yavas 2007	Turkey	No	Not reported	Reported; no CoI	Not registered	No
32	Yung 2007	USA	No	Not reported	Not reported	Not registered	No
33	Zaczek 2014	Sweden	No	Industry/Non‐industry	Reported; no CoI	Not registered	No
34	Zhang 2008	China	No	Not reported	Not reported	Not registered	No
CoI: conflict of interest

Table 2. Studies

Ir a la tabla de la revisión

Table 3. Participant numbers

	Study	Number of people randomised	Number of people randomised (missing data imputed)*	Number of eyes	Number of eyes estimated (missing data imputed)*	Number of people followed up	Number of people followed up (missing data imputed)*	Percentage follow‐up	Eyes per person enrolled in the trial
1	Almeida 2008	98	98	106	106	‐	74	75%	106 eyes of 98 people
2	Almeida 2012	193	193	‐	193	162	162	84%	Probably one
3	Asano 2008	150	150	150	150	142	142	95%	One eye
4	Brown 1996	‐	‐	‐	‐	‐		‐	Probably one
5	Cervantes‐Coste 2009	60	60	60	60	60	60	100%	One eye
6	Chatziralli 2011	145	145	145	145	138	138	95%	Probably one
7	Donnenfeld 2006	100	100	‐	100	‐	100	‐	Unclear
8	Elsawy 2013	70	70	86	86	‐	86	‐	86 eyes of 70 patients
9	Endo 2010	75	75	75	75	62	62	83%	One eye
10	Italian Diclofenac Study Group 1997	281	281	281	281	229	229	81%	One eye
11	Jung 2015	91	91	91	91	Not reported	91	Not reported	One eye
12	Kraff 1982	500	500	‐	500	492	492	98%	Unclear
13	Li 2011	217	217	217	217	‐	217	‐	One eye
14	Mathys 2010	84	84	84	84	79	79	94%	One eye
15	Miyake 2007	62	62	62	62	50	50	81%	Probably one
16	Miyake 2011	60	60	60	60	55	55	92%	One eye
17	Miyanaga 2009	72	72	72	72	‐	72	‐	One eye
18	Moschos 2012	79	79	79	79	‐	79	‐	One eye
19	Quentin 1989	179	179	179	179	112	112	63%	One eye
20	Rossetti 1996	88	88	88	88	‐	88	‐	Probably one
21	Singh 2012	263	263	263	263	251	251	95%	One eye
22	Solomon 1995	681	681	681	681	364	364	53%	Probably one
23	Tauber 2006	‐	32	‐	32	32	32	‐	Unclear
24	Ticly 2014	91	91	91	91	81	81	89%	Probably one
25	Tunc 1999	75	75	75	75	75	75	‐	One eye
26	Tzelikis 2015	142	142	142	142	126	126	89%	One eye
27	Umer‐Bloch 1983	‐	73	‐	73	73	73	‐	Unclear
28	Wang 2013	240	240	‐	240	167	167	70%	Unclear
29	Wittpenn 2008	546	546	546	546	478	478	88%	One eye
30	Yannuzzi 1981	‐	201	231	231	‐	231	59%	231 eyes of 210 people
31	Yavas 2007	189	189	189	189	179	179	95%	One eye; right eye only
32	Yung 2007	37	37	‐	37	‐	37	‐	Unclear
33	Zaczek 2014	160	160	160	160	152	152	95%	One eye
34	Zhang 2008	‐	198	220	220	‐	220	100%	220 eyes of 198 people
*For studies that did not report the number randomised, we have estimated this from the number followed up. For studies that did not report the number followed up, we have estimated this from the numbers randomised. Number of eyes estimated assuming one eye per person, if not clearly stated otherwise.

Table 3. Participant numbers

Ir a la tabla de la revisión

Table 4. Participant characteristics

	Study	Average age	Age range	% female	% with diabetes	% with uveitis
1	Almeida 2008	72	45 to 92	61%	21%	1%
2	Almeida 2012	72	50 to 88	54%	‐ but low risk population	"low risk population"
3	Asano 2008	66	‐	56%	0% people with diabetes excluded	0% people with uveitis excluded
4	Brown 1996	‐	‐	‐	‐ but people with DR excluded	0% people with uveitis excluded
5	Cervantes‐Coste 2009	72	51 to 88	64%	20%	0% people with uveitis excluded
6	Chatziralli 2011	74	‐	40%	10%	0% people with uveitis excluded
7	Donnenfeld 2006	73	‐	55%	0% people with diabetes excluded	0% people with uveitis excluded
8	Elsawy 2013	‐	‐	37%	100%	‐
9	Endo 2010	69	37 to 84	45%	100%	0% people with uveitis excluded
10	Italian Diclofenac Study Group 1997	68	‐	52%	‐	‐
11	Jung 2015	67	‐	55%	26%	‐
12	Kraff 1982	69	37 to 97	57%	‐	‐
13	Li 2011	72	‐	63%	100%	‐
14	Mathys 2010	72	44 to 90	54%	0% people with diabetes excluded	0% people with uveitis excluded
15	Miyake 2007	66	‐	54%	0% people with diabetes excluded	0% people with uveitis excluded
16	Miyake 2011	65	48 to 82	46%	9%	0% people with uveitis excluded
17	Miyanaga 2009	72	41 to 86	71%	0% people with diabetes excluded	0% people with uveitis excluded
18	Moschos 2012	77	‐	66%	0% people with diabetes excluded	0% people with uveitis excluded
19	Quentin 1989	73	‐	55%	‐ but people with DR excluded	0% people with uveitis excluded
20	Rossetti 1996	74	‐	64%	0% people with diabetes excluded	‐
21	Singh 2012	67	32 to 87	63%	100%	0% people with uveitis excluded
22	Solomon 1995	68	39 to 100	53%	‐	0% people with uveitis excluded
23	Tauber 2006	‐	‐	‐	‐	‐
24	Ticly 2014	67	‐	47%	0% people with diabetes excluded	0% people with uveitis excluded
25	Tunc 1999	61	‐	39%	0% people with diabetes excluded	0% people with uveitis excluded
26	Tzelikis 2015	‐	‐	‐	‐	‐
27	Umer‐Bloch 1983	69	‐	52%	‐ but people with DR excluded	0% people with uveitis excluded
28	Wang 2013	73	46 to 92	54%	0% people with diabetes excluded	0% people with uveitis excluded
29	Wittpenn 2008	70	‐	53%	‐	‐
30	Yannuzzi 1981	‐	‐	‐	‐	‐
31	Yavas 2007	65	‐	40%	0% people with diabetes excluded	0% people with uveitis excluded
32	Yung 2007	‐	‐	‐	100%	‐
33	Zaczek 2014	69	‐	65%	‐	‐
34	Zhang 2008	‐	‐	‐	‐	‐
DR: diabetic retinopathy

Table 4. Participant characteristics

Ir a la tabla de la revisión

Table 5. Interventions

	Study	Type of cataract surgery	Comparison	NSAIDs	Steroid	Placebo in comparator group	Type of placebo
1	Almeida 2008	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.5%	Prednisolone 1%	No	‐
2	Almeida 2012	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.5%, Nepafenac 0.1%	Prednisolone 1%	Yes	Sterile saline drops
3	Asano 2008	Phacoemulsification	NSAIDs versus steroids	Diclofenac 0.1%	Betamethasone 0.1%	No	‐
4	Brown 1996	Phacoemulsification	NSAIDs versus steroids	Diclofenac 0.1%	Prednisolone 1%	No	‐
5	Cervantes‐Coste 2009	Phacoemulsification	NSAIDs plus steroids versus steroids	Nepafenac 0.1%	Dexamethasone (combined with tobramycin)	No	‐
6	Chatziralli 2011	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.5%	Dexamethasone 0.1% (combined with tobramycin 0.3%)	No	‐
7	Donnenfeld 2006	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%	Prednisolone 1%	Yes	Vehicle
8	Elsawy 2013	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%	Dexamethasone 0.1%,	No	‐
9	Endo 2010	Phacoemulsification	NSAIDs versus steroids	Bromfenac	Betamethasone (with fradiomycin sulfate) followed by fluorometholone	No	‐
10	Italian Diclofenac Study Group 1997	ECCE	NSAIDs versus steroids	Diclofenac 0.1%	Dexamethasone 0.1%	Yes	Not specified
11	Jung 2015	Phacoemulsification	NSAIDs versus steroids	Bromfenac 0.1%, Ketorolac 0.4%	Prednisolone acetate 1%	No	‐
12	Kraff 1982	ECCE and phacoemulsification	NSAIDs plus steroids versus steroids	Indomethacin	Dexamethasone (in combination with neomycin sulfate, polymyxin B sulfate) for 4 days followed by dexamethasone alone for 4 weeks followed by fluorometholone for at least 6 months	Yes	Vehicle
13	Li 2011	Phacoemulsification	NSAIDs plus steroids versus steroids	Diclofenac 1%	Dexamethasone (combined with tobramycin)	No	‐
14	Mathys 2010	Phacoemulsification	NSAIDs plus steroids versus steroids	Nepafenac 0.1%	Prednisolone 1%	No	‐
15	Miyake 2007	Phacoemulsification	NSAIDs versus steroids	Diclofenac 0.1%	Fluorometholone 0.1%	No	‐
16	Miyake 2011	Phacoemulsification	NSAIDs versus steroids	Nepafenac 0.1%	Fluorometholone 0.1%	No	‐
17	Miyanaga 2009	Phacoemulsification	NSAIDs plus steroids versus steroids/NSAIDs versus steroids	Bromfenac 0.1%	Betamethasone 0.1%, fluorometholone	No	‐
18	Moschos 2012	Phacoemulsification	NSAIDs plus steroids versus steroids	Diclofenac 0.1%	Dexamethasone 0.1% (combined with chloramphenicol 0.5%)	No	‐
19	Quentin 1989	ICCE	NSAIDs plus steroids versus steroids	Diclofenac 0.1%	Dexamethasone	Yes	Not specified
20	Rossetti 1996	ECCE	NSAIDs plus steroids versus steroids	Diclofenac	Dexamethasone (combined with tobramycin)	Yes	Not specified
21	Singh 2012	Phacoemulsification	NSAIDs plus steroids versus steroids	Nepafenac 1%	Prednisolone	Yes	Vehicle
22	Solomon 1995	ECCE	NSAIDs plus steroids versus steroids	Flurbiprofen 0.03% Indomethacin 1%	Prednisolone	Yes	Vehicle
23	Tauber 2006	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%	Prednisolone 1%	No	‐
24	Ticly 2014	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%	Prednisolone 1%	Yes	Dextran 70/hypromellose
25	Tunc 1999	ECCE	NSAIDs plus steroids versus steroids	Diclofenac 0.1%	Dexamethasone 1%	No	‐
26	Tzelikis 2015	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%, Nepafenac 0.1%	Prednisolone 1%	Yes	Artificial tears
27	Umer‐Bloch 1983	ECCE/ICCE	NSAIDs plus steroids versus steroids	Indomethacin 1%	Dexamethasone (combined with either chloramphenicol or neomycin)	Yes	Vehicle
28	Wang 2013	Phacoemulsification	NSAIDs plus steroids versus steroids	Bromfenac 0.1%	fluorometholone 0.1% and dexamethasone 0.1%	No	‐
29	Wittpenn 2008	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.4%	Prednisolone 1%	Yes	Artificial tears
30	Yannuzzi 1981	ICCE	NSAIDs plus steroids versus steroids	Indomethacin 1%	Steroids given as part of standard care, not specified exactly what	Yes	Vehicle
31	Yavas 2007	Phacoemulsification	NSAIDs plus steroids versus steroids	Indomethacin 0.1%	Prednisolone 1%	No	‐
32	Yung 2007	Phacoemulsification	NSAIDs plus steroids versus steroids	Ketorolac 0.5%	Prednisolone 1%	Yes	Artificial tears
33	Zaczek 2014	Phacoemulsification	NSAIDs plus steroids versus steroids	Nepafenac 0.1%	Dexamethasone 0.1%	Yes	Artifical tears
34	Zhang 2008	Phacoemulsification	NSAIDs plus steroids versus steroids	Pranoprofen	Dexamethasone (combined with tobramycin)	No	‐
ECCE: extracapsular cataract extraction ICCE: intracapsular cataract extraction NSAIDs: non‐steroidal anti‐inflammatory drugs

Table 5. Interventions

Ir a la tabla de la revisión

Table 6. Outcomes

		Poor vision outcome due to MO	Quality of life/patient satisfaction	Central retinal thickness	Adverse effects reported	CMO	Inflammation	BCVA	Additional outcomes
Study	Follow‐up	Analysis 1.1	No analysis; only one study reported this	Analysis 1.2; Analysis 2.1	Table 7	Analysis 1.4; Analysis 2.2	Analysis 1.5; Analysis 1.6; Analysis 2.3	Analysis 1.7; Analysis 2.4	Analysis 1.3
Almeida 2008	1 month				Yes	OCT used but CMO not defined			Change in total macular volume
Almeida 2012	1 month		COMTOL questionnaire	Mean change reported but not possible to calculate SD				LogMAR	Change in total macular volume; change in average macular cube thickness
Asano 2008	8 weeks				Yes	Fluorescein angiography using Miyake 1977 classification (at 5 weeks only)	Laser flare‐cell photometry, mean value of anterior chamber flare (photons/millisecond)	LogMAR, final value
Brown 1996	1 month						Laser flare‐cell photometry, mean value of anterior chamber flare reported (photons) but was not possible to calculate SD
Cervantes‐Coste 2009	6 weeks	Quote: "None of the patients developed clinically significant macular oedema associated with vision loss"		Final value	Yes	Only reported CMO associated with vision loss	"Inflammatory cells greater than 1+ during first week of postoperative visits"		Total macular volume
Chatziralli 2011	6 weeks	Fundoscopy and Amsler grid test Quote: "no evidence of clinically significant CME"			Yes	"No evidence of clinically significant CME was detected in any patient via fundoscopy and the Amsler grid test"	Corneal oedema or Tyndall reaction or conjunctival hyperaemia	LogMAR, final value
Donnenfeld 2006	3 months				Yes	"Clinically significant CME" but otherwise not defined, at 2 weeks only	"Mean inflammation score" but was not possible to calculate SD	LogMAR, final value but could not extract data on SD
Elsawy 2013	12 weeks					Clinical examination, unclear if OCT‐verified
Endo 2010	6 weeks			Final value	Yes		Anterior chamber flare values, photon count per millisecond	LogMAR, final value
Italian Diclofenac Study Group 1997	140 days				Yes	Fluorescein angiography using Miyake 1977 classification
Jung 2015	1 month			Change	Yes		"Inflammatory score" (sum of anterior chamber cells and flare grade"		Change in macular volume
Kraff 1982	Between 2.5 and 12 months				Yes	Fluorescein angiography using Miyake 1977 classification		Snellen acuity only, not included in analyses
Li 2011	1 month			Final value		OCT, "clinically apparent" CME otherwise not defined		Snellen acuity only, not included in analyses
Mathys 2010	2 months			Change from baseline	Yes			LogMAR	Change in foveal thickness, change in macular volume
Miyake 2007	5 weeks					Fluorescein angiography using Miyake 1977 classification	Unit of measurement unclear	Snellen acuity only, not included in analyses
Miyake 2011	5 weeks			Final value	Yes	Fluorescein angiography using Miyake 1977 classification	Flare (photons/millisec), final value		Change in logMAR BCVA, categorical 3+, 2, 1 lines increase and no change
Miyanaga 2009	2 months				Yes	"Obvious CMO confirmed by OCT"	Aqueous flare (photons/millisecond)	LogMAR, final value
Moschos 2012	1 month			Final value				LogMAR, final value
Quentin 1989	180 days				Yes	Fluorescein angiography using Miyake 1977 classification		Snellen acuity only, not included in analyses
Rossetti 1996	6 months				Yes	Fluorescein angiography using Miyake 1977 classification		Snellen acuity only, not included in analyses
Singh 2012	90 days			Change from baseline	Yes	">= 30% increase in central subfield macular thickness from baseline"	Flare mentioned but data not reported	Corrected BCVA loss of more than 5 letters from day 7 postop
Solomon 1995	6 months	Days 21 to 60, MO = positive angiography and visual acuity <= 20/40			Yes	Fluorescein angiography using classification***		Snellen acuity but not reported by treatment group
Tauber 2006	30 days (3 months mentioned but not reported)			Reported but no mean/SD					Proportion with > 10% increase in retinal thickness
Ticly 2014	5 weeks			Final value	Yes	Fluorescein angiography using Miyake 1977 classification		LogMAR
Tunc 1999	2 months					Fluorescein angiography 0 no leakage (CME absent),1 oedema less than perifoveal, 2 mild perifoveal oedema, 3 moderate perifoveal oedema (approx. 1 disc diameter), 4 severe perifoveal oedema plus drop of 1 line of Snellen acuity since second postoperative week defined as "clinically significant"
Tzelikis 2015	12 weeks			Final value	Yes			LogMAR, final value (at 30 days only)
Umer‐Bloch 1983	12 weeks				Yes	Fluorescein angiography using Miyake 1977 classification		Snellen acuity only, not included in analyses
Wang 2013	2 months	OCT‐confirmed CMO with "visual impairment" (not specified cutpoint)		Final value	Yes	"CME was defined as central retinal thickness > 250 μm and the presence of intraretinal cystoid space beneath the foveal, with the diagnosis confirmed by the same retinal specialist"	Mean photon count values	LogMAR, final value
Wittpenn 2008	4 weeks	OCT‐confirmed CMO with visual acuity < 6/9			Yes	Clinical and OCT‐based
Yannuzzi 1981	1 year	CMO on fluorescein angiography with visual acuity < 6/60			Yes	Fluorescein angiography, evidence but not defined
Yavas 2007	3 months					"Slight fluorescein leakage into the cystic space without enclosing the entire central fovea or complete fluorescein accumulation in the cystic space was diagnosed as angiographic CME"		LogMAR, final value
Yung 2007	12 weeks
Zaczek 2014	6 weeks				Yes	OCT‐verified but not defined	Mean anterior chamber flare reported in figure but no SD	LogMAR, final value	Change in total macular volume
Zhang 2008	1 month					OCT‐verified but not defined	Tyn granule +
BCVA: best corrected visual acuity CME: cystoid macular oedema (edema) CMO: cystoid macular oedema COMTOL: Comparison of Ophthalmic Medications for Tolerability (questionnaire) MO: macular oedema OCT: ocular coherence tomography SD: standard deviation

Table 6. Outcomes

Ir a la tabla de la revisión

Table 7. Adverse effects

Study	Follow‐up	Number of people followed up	Adverse effects
Almeida 2008	1 month	74	Quote: "There were 3 dropouts in the treatment group related to ketorolac corneal toxicity, most notably pain attributed to the drops."
Almeida 2012	1 month	162	Quote: “One patient in the ketorolac group was hospitalized with a cardiovascular event and could not complete the follow‐up. Finally, 1 patient on nepafenac had side effects of ocular redness and irritation and could not continue with the study.”
Asano 2008	8 weeks	142	2 "complications" not specified.
Brown 1996	1 month	NR	Adverse effects not reported.
Cervantes‐Coste 2009	6 weeks	60	Quote: "There were no serious treatment‐related adverse events or toxicity related to the use of nepafenac 0.1%."
Chatziralli 2011	6 weeks	138	Quote: "All patients reported pain and ocular discomfort lower than 1/10 on the visual analog scale at all time points."
Donnenfeld 2006	2 weeks	100	Quote: "Use of ketorolac 0.4% for 1 or 3 days provided decreased levels of patient discomfort intraoperatively and postoperatively. Intraoperatively, 3 days of ketorolac 0.4% provided significantly lower discomfort scores than with 1‐hour and placebo dosing (P < 0.001). One day of ketorolac 0.4% also provided significantly reduced intraoperative discomfort scores than with 1‐hour dosing (P = 0.001) and placebo dosing (P < 0.001). Postoperatively, 3 days of ketorolac 0.4% provided significantly lower discomfort scores than 1‐hour dosing or control dosing (P < 0.001) (Figure 5). In addition, patients randomised to 1 or 3 days of ketorolac 0.4% were significantly less likely to require additional intravenous anesthesia (8% in each group) than patients in the control group (40%) (P = 0.008). Twenty percent of patients in the 1‐hour group required additional anesthesia for pain control."
Elsawy 2013	12 weeks	86	Adverse effects not reported.
Endo 2010	6 weeks	62	Quote: "No adverse events were noted in either group."
Italian Diclofenac Study Group 1997	140 days	229	Quote: "No major adverse effects were noted in either group." "Subjective tolerance of the two treatments was good and remained similar throughout the study, although a trend towards increased burning was seen in the diclofenac group."
Jung 2015	1 month	91	Quote: "There were no adverse events except for a mild burning sensation in one patient in the ketorolac group; the symptom was tolerable and did not lead to discontinuation of the medication."
Kraff 1982	between 2.5 and 12 months	492	Quote: "There were no complications that could be ascribed to the use of topical indomethacin other than minor stinging and burning noted by the patients."
Li 2011	1 month	217	Adverse effects not reported.
Mathys 2010	2 months	79	Quote: "There were no adverse events reported by patients using nepafenac."
Miyake 2007	5 weeks	50	Adverse effects not reported.
Miyake 2011	5 weeks	55	NSAIDs: 6 adverse effects: decreased lacrimation, conjunctivitis allergic, abnormal sensation in eye, vomiting (2), constipation. Steroid group: 9 adverse effects: decreased lacrimation, conjunctivitis allergic, retinal haemorrhage, keratoconjunctivitis sicca, chorioretinopathy, influenza, insomnia, diarrhoea, humeral fracture.
Miyanaga 2009	2 months	72	Adverse effects not reported.
Moschos 2012	1 month	79	Adverse effects not reported.
Quentin 1989	180 days	112	Quote: "Diclofenac group: two patients were feeling burning after application of eye drops during the stationary care, for placebo: none. In both groups burning was reported later on in the examinations."
Rossetti 1996	6 months	88	Quote: "Treatment regimens were well tolerated with no evidence of relevant side effects."
Singh 2012	90 days	251	Quote: "No patient deaths were reported during the study. Overall, 13 patients reported other serious adverse events, none of which were related to treatment. Three of the serious adverse events reported in the vehicle group (cardiac failure congestive, coronary artery occlusion, and pancreatitis) led to patient discontinuation; no other serious adverse events led to discontinuation in either treatment group. Separate from the three patients who discontinued due to serious adverse events, four other patients discontinued study participation due to nonserious adverse events. Of these nonserious events, two reported instances of punctate keratitis (one in each treatment group) were assessed as being related to the study drugs. No instances of targeted adverse events (defined as corneal erosions) were reported during the study. Two reports of punctate keratitis and a single report of corneal epithelium defect were assessed as being related to treatment with nepafenac. A single report of punctate keratitis was assessed as being related to treatment with vehicle. No other ocular or nonocular adverse events reported in the study were assessed as being related to the study drugs. In both treatment groups, corneal staining and intraocular pressure were each generally similar at the presurgical baseline and at the day 90 visit (or early exit). Additionally, no safety issues or trends were identified based upon changes from baseline in fundus parameters (retina/macula/choroid and optic nerve) and ocular signs (inflammatory cells, aqueous flare, corneal oedema, and bulbar conjunctival injection). The study results indicate no new clinically relevant risks associated with increasing the dosing of nepafenac from 14 days to 90 days, even in the higher‐risk diabetic patient population."
Solomon 1995	6 months	364	Quote: "During the study, the mean severity of foreign‐body sensation, pain, photophobia, and tearing did not become more than mild (1 +) in any treatment group. This was also true of burning and stinging following treatment instillation (Figure 4). The severity of burning and stinging was significantly greater in the flurbiprofen group on days 4‐20 and 21‐60 and in the indomethacin group on days 1‐3, 4‐20, 21‐60, and 61‐120 than in the vehicle group. At day 1‐3, moderate to severe burning and stinging were reported by 7.0% (16/230) of the patients treated with flurbiprofen, 9.7% (23/237) of the patients treated with indomethacin, and 3.1% (7/224) of the patients treated with vehicle."
Tauber 2006	30 days (3 months mentioned but not reported)	32	Adverse effects not reported.
Ticly 2014	5 weeks	81	One patient withdrew because of burning.
Tunc 1999	2 months	75	Adverse effects not reported.
Tzelikis 2015	1 month	126	Quote: "There were no adverse side effects in either group."
Umer‐Bloch 1983	12 weeks	73	Quote from translation: "40% reported a short burning after using indomethacin eye drops, only rare in patients of the placebo group. One patient had 6 weeks after treatment an allergic blepharitis due to indomethacin. Long‐term: 52 patients were followed for 6 months and 34 patients one year. 4 patients with indomethacin had visual acuity reduction because of a clinically new cystoid edema; 2 of these patients had spontaneous healing after 4‐6 weeks, the other 2 edema cases did not resolve. 2 patients had a new senile macula pathology, and 2 patients had a retinal detachment due to aphakia. Placebo: 2 patients still had an edema after 12 weeks, while one patient developed a new edema later."
Wang 2013	2 months	167	Quote: "No drug‐related adverse events were identified."
Wittpenn 2008	4 weeks	478	Quote: "The most commonly reported adverse events (investigator self‐report) in the ketorolac/steroid group were burning/stinging/tearing (4/268). Transient elevations in intraocular pressure (IOP) were the most commonly reported adverse event in the steroid group (3/278). There were two serious adverse events, both in the steroid group: one patient developed endophthalmitis and one patient died (cause determined to be unrelated to the study medication)."
Yannuzzi 1981	1 year	231	Adverse effects not reported.
Yavas 2007	3 months	179	Adverse effects not reported.
Yung 2007	12 weeks	37	Adverse effects not reported.
Zaczek 2014	6 weeks	152	Quote: "Mild to moderate punctuate epithelial defects of the cornea were found in both groups 3 weeks after treatment.Statistically significantly more patients in the nepafenac group than in the control group had corneal fluorescein staining (20 [26.7%] versus 8 [10.4%]) (PZ.0119). Headache was reported by 3 patients (4.0%) in the nepafenac group and 2 patients (2.6%) in the control group (PZ.9750). No other systemic or local untoward effects were recorded during 3 weeks of treatment in either study group."
Zhang 2008	1 month	220	Adverse effects not reported.

Table 7. Adverse effects

Ir a la tabla de la revisión

Comparison 1. NSAIDs plus steroids versus steroids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Poor vision due to MO Show forest plot	6		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

1.1 3 months	5	1360	Risk Ratio (M‐H, Random, 95% CI)	0.41 [0.23, 0.76]
1.2 12 months	1	88	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.09, 20.37]
2 Central retinal thickness Show forest plot	9		Mean Difference (IV, Random, 95% CI)	Totals not selected

2.1 Change from baseline	3		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
2.2 FInal value	6		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
3 Total macular volume Show forest plot	6	570	Mean Difference (IV, Random, 95% CI)	‐0.14 [‐0.21, ‐0.07]

4 Macular oedema Show forest plot	21	3638	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.32, 0.49]

5 Inflammation Show forest plot	3		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

6 Inflammation (flare) Show forest plot	2	216	Mean Difference (IV, Fixed, 95% CI)	‐1.41 [‐2.30, ‐0.52]

7 BCVA Show forest plot	10		Mean Difference (IV, Random, 95% CI)	Totals not selected

7.1 Final value	7		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]
7.2 Change from baseline	3		Mean Difference (IV, Random, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. NSAIDs plus steroids versus steroids

Ir a la tabla de la revisión

Comparison 2. NSAIDs versus steroids

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Central retinal thickness Show forest plot	2	121	Mean Difference (IV, Fixed, 95% CI)	‐22.64 [‐38.86, ‐6.43]

2 Macular oedema Show forest plot	5	520	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.18, 0.41]

3 Inflammation (flare) Show forest plot	5		Mean Difference (IV, Random, 95% CI)	Totals not selected

4 BCVA Show forest plot	3		Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 2. NSAIDs versus steroids

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet