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Ácidos grasos omega 3 para prevenir o enlentecer la progresión de la degeneración macular senil

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor Macular Degeneration
#2 MeSH descriptor Retinal Degeneration
#3 MeSH descriptor Retinal Neovascularization
#4 MeSH descriptor Choroidal Neovascularization
#5 MeSH descriptor Macula Lutea
#6 macula* near lutea*
#7 (macula* or retina* or choroid*) near/4 degenerat*
#8 (macula* or retina* or choroid*) near/4 neovascul*
#9 maculopath*
#10 AMD or ARMD or CNV
#11 (#1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10)
#12 MeSH descriptor Fatty Acids, Omega‐3
#13 fatty near/2 acid*
#14 omega 3
#15 polyunsaturated
#16 LCPUFA* or PUFA*
#17 docosahexaenoic or DHA*
#18 eicosapentaenoic or EPA*
#19 (#12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18)
#20 (#11 AND #19)

Appendix 2. MEDLINE (OvidSP) search strategy

1. randomized controlled trial.pt.
2. (randomized or randomised).ab,ti.
3. placebo.ab,ti.
4. dt.fs.
5. randomly.ab,ti.
6. trial.ab,ti.
7. groups.ab,ti.
8. or/1‐7
9. exp animals/
10. exp humans/
11. 9 not (9 and 10)
12. 8 not 11
13. exp retinal degeneration/
14. retinal neovascularization/
15. choroidal neovascularization/
16. exp macula lutea/
17. maculopath$.tw.
18. ((macul$ or retina$ or choroid$) adj3 degener$).tw.
19. ((macul$ or retina$ or choroid$) adj3 neovasc$).tw.
20. (AMD or ARMD or CNV).tw.
21. or/13‐20
22. Fatty Acids, Omega‐3/
23. (fatty adj2 acid$).tw.
24. omega 3.tw.
25. polyunsaturated.tw.
26. (LCPUFA$ or PUFA$).tw.
27. (docosahexaenoic or DHA$).tw.
28. (eicosapentaenoic or EPA$).tw.
29. or/22‐28
30. 21 and 29
31. 12 and 30

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

Appendix 3. EMBASE (OvidSP) search strategy

1. exp randomized controlled trial/
2. exp randomization/
3. exp double blind procedure/
4. exp single blind procedure/
5. random$.tw.
6. or/1‐5
7. (animal or animal experiment).sh.
8. human.sh.
9. 7 and 8
10. 7 not 9
11. 6 not 10
12. exp clinical trial/
13. (clin$ adj3 trial$).tw.
14. ((singl$ or doubl$ or trebl$ or tripl$) adj3 (blind$ or mask$)).tw.
15. exp placebo/
16. placebo$.tw.
17. random$.tw.
18. exp experimental design/
19. exp crossover procedure/
20. exp control group/
21. exp latin square design/
22. or/12‐21
23. 22 not 10
24. 23 not 11
25. exp comparative study/
26. exp evaluation/
27. exp prospective study/
28. (control$ or prospectiv$ or volunteer$).tw.
29. or/25‐28
30. 29 not 10
31. 30 not (11 or 23)
32. 11 or 24 or 31
33. exp retina degeneration/
34. retina neovascularization/
35. subretinal neovascularization/
36. exp retina macula lutea/
37. maculopath$.tw.
38. ((macul$ or retina$ or choroid$) adj3 degener$).tw.
39. ((macul$ or retina$ or choroid$) adj3 neovasc$).tw.
40. (AMD or ARMD or CNV).tw.
41. or/33‐40
42. omega 3 fatty acid/
43. (fatty adj2 acid$).tw.
44. omega 3.tw.
45. polyunsaturated.tw.
46. (LCPUFA$ or PUFA$).tw.
47. docosahexaenoic acid/
48. (docosahexaenoic or DHA$).tw.
49. icosapentaenoic acid/
50. (eicosapentaenoic or EPA$).tw.
51. or/42‐50
52. 41 and 51
53. 32 and 52

Appendix 4. LILACS search strategy

macular degenerat$ or AMD or AMRD or CNV and omega or fatty acid or polyunsaturated or docosahexaenoic or eicosapentaenoic

Appendix 5. metaRegister of Controlled Trials search strategy

(macular degeneration) AND omega

Appendix 6. ClinicalTrials.gov search strategy

(Macular Degeneration) AND Omega 3

Appendix 7. ICTRP search strategy

(Macular Degeneration) AND Omega 3

Results from searching for studies for inclusion in the review.
Figures and Tables -
Figure 1

Results from searching for studies for inclusion in the review.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

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

Forest plot of comparison (Analysis 1.1): 1 Omega 3 fatty acids versus control, outcome: 1.10 Progression of AMD.
Figures and Tables -
Figure 4

Forest plot of comparison (Analysis 1.1): 1 Omega 3 fatty acids versus control, outcome: 1.10 Progression of AMD.

Comparison 1 Omega 3 fatty acids versus control, Outcome 1 Progression of AMD.
Figures and Tables -
Analysis 1.1

Comparison 1 Omega 3 fatty acids versus control, Outcome 1 Progression of AMD.

Summary of findings for the main comparison. Omega 3 fatty acids compared to placebo for slowing the progression of age‐related macular degeneration

Omega 3 fatty acids compared to placebo for slowing the progression of age‐related macular degeneration

Patient or population: people with AMD
Settings: community
Intervention: omega 3 fatty acids
Comparison: no omega 3 fatty acids (placebo)

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

No omega 3 fatty acids (placebo)

Omega 3 fatty acids

Loss of 3 or more lines of VA at 24 months

100 per 1000

114 per 1000
(53 to 245)

RR 1.14, 95% CI 0.53 to 2.45

236
(1 study)

⊕⊕⊕⊝
moderate1

Loss of 3 or more lines of VA at 36 months

150 per 1000

187 per 1000
(104 to 339)

RR 1.25, 95% CI 0.69 to 2.26)

230
(1 study)

⊕⊕⊕⊝
moderate1

Incidence of CNV at 24 months

100 per 1000

106 per 1000
(47 to 240)

RR 1.06, 95% CI 0.47 to 2.40

224
(1 study)

⊕⊕⊕⊝
moderate1

Incidence of CNV at 36 months

150 per 1000

168 per 1000
(80 to 357)

RR 1.12, 95% CI 0.53 to 2.38

195
(1 study)

⊕⊕⊕⊝
moderate1

Progression of AMD over 5 years

300 per 1000

290 per 1000
(259 to 325)

HR 0.96
(0.84 to 1.1)

2343
(2 studies)

⊕⊕⊕⊕
high

Adverse effects

500 per 1000

505 per 1000
(470 to 545)

RR 1.01, 95% CI 0.94 to 1.09

2343
(2 studies)

⊕⊕⊕⊕
high

AREDS2 reported participants with one or more serious adverse events (AE). NAT‐2 reported total AE including treatment emergent and serious non‐ocular events

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; OR: Odds ratio; HR: Hazard ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 Downgraded for imprecision

Figures and Tables -
Summary of findings for the main comparison. Omega 3 fatty acids compared to placebo for slowing the progression of age‐related macular degeneration
Table 1. Adverse effects

Adverse effects

Omega 3

N (%)

Placebo

N (%)

AREDS 2

Total number of participants

N = 1068

N = 1012

Participants with ≥ 1 adverse event

· Cardiac disorders

· Gastrointestinal disorders

· Infections

· Neoplasms

· Nervous system disorders

· Respiratory and chest disorders

505 (47.3)

119 (11.1)

58 (5.4)

103 (9.6)

83 (7.8)

72 (6.7)

37 (3.5)

479 (47.3)

96 (9.5)

76 (7.5)

90 (8.9)

80 (7.9)

66 (6.5)

44 (4.3)

NAT‐2

Total number of participants

N = 134

N = 129

Total adverse events

· Treatment emergent adverse events*

· Ocular

· Serious non‐ocular

125 (83.3)

5 (4.7)

88 (58.4)

31 (23.1)

115 (77.7)

2 (1.6)

74 (50.0)

30 (23.6)

* As defined by the study authors (including gastrointestinal disorders, allergic dermatitis and breath odour)

Figures and Tables -
Table 1. Adverse effects
Comparison 1. Omega 3 fatty acids versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Progression of AMD Show forest plot

2

Hazard Ratio (Fixed, 95% CI)

0.96 [0.84, 1.10]

Figures and Tables -
Comparison 1. Omega 3 fatty acids versus control