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Supplementary Material

Figure S1: Updated search strategy to identify evidence on AMD and the

specified interventions and comparators in Ovid MEDLINE

1 retinal degeneration/ or exp macular degeneration/ (25843)2 Retinal Neovascularization/ (2346)3 Choroidal Neovascularization/ (4331)4 exp Macula Lutea/ (10610)5 maculopath$.ti,ab,kf. (3309)6 ((macula$ or retina$ or sub-retina$ or choroid$) adj3 (degener$ or neovascula$ or neo-vascula$)).ti,ab,kf. (26136)7 (macula$ adj3 lutea).ti,ab,kf. (400)8 (AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV or nAMD).ti,ab,kf. (13780)9 or/1-8 (54123)10 Vascular Endothelial Growth Factor A/ (38654)11 angiogenesis inhibitors/ (18444)12 antibodies, monoclonal, humanized/ (28873)13 bevacizumab/ (7825)14 ranibizumab/ (1920)15 photosensitizing agents/ (11222)16 phototherapy/ or exp photochemotherapy/ (20374)17 (aflibercept or eylea$ or zaltrap$ or trapeye$ or trap-eye$ or 862111-32-8 or "862111328" or 8621-11-328 or 862111-328 or 862-111-328).ti,ab,rn,kf. (714)18 (ranibizumab or lucentis$ or rhufab$ or 347396-82-1 or "347396821" or 347396-821 or 347-396-821 or 3473-96-821).ti,ab,rn,kf. (2694)19 (bevacizumab or avastin$ or 216974-75-3 or "216974753" or 216974-753 or 216-974-753 or 2169-74-753).ti,ab,rn,kf. (11929)20 (photodynamic$ or photo-dynamic$ or phototherap$ or photo-therap$ or photosensiti$ or photo-sensiti$ or photochemotherap$ or photo-chemotherap$ or pdt).ti,ab,kf. (39844)21 porphyrins/ (14851)22 (verteporfin or visudyne$ or benzoporphyrin or porphyrin or 129497-78-5 or "129497785" or 129497-785 or 129-497-785 or 1294-97-785).ti,ab,rn,kf. (15453)

1

1

2

3

4

56789

10111213141516171819202122232425262728293031323334353637

23 (fovista or E10030 or anti-PDGF or antiPDGF or anti-platelet derived growth factor$1 or antiplatelet derived growth factor$1 or pegpleranib).ti,ab,rn,kf. (341)24 or/10-23 (142433)25 9 and 24 (7590)26 exp animals/ not humans/ (4189142)27 25 not 26 (6845)

We also searched the following congress abstracts on 1 March 2016 (full details are

provided in Appendix A): American Association of Ophthalmology (AAO) congress

abstracts (2013-2016); Association for Research in Vision and Ophthalmology

(ARVO) congress abstracts (2013-2016); European Society of Retina Specialists

(EURETINA) congress abstracts (2013-2016); and we assessed the reference lists

of relevant reviews to identify any studies missed by the database searches.

2

38394041424344

45

46

47

48

49

50

51

5253

Table S1. Information sources searched for the review

Database InterfaceDate searched

MEDLINE and MEDLINE In-Process

OvidSP 25/2/16

EMBASE OvidSP 25/2/16

Cochrane Database of Systematic Reviews (CDSR)

Cochrane Library/Wiley Interscience

25/2/16

Cochrane Central Register of Controlled Trials (CENTRAL)


25/2/16

DARE Database of Abstracts of Reviews of Effects (DARE)


25/2/16

Health Technology Assessment Database (HTA)


25/2/16

Science Citation Index (SCI) and Conference Proceedings Citation Index – Science (CPCI-S)

Web of Science 25/2/16

Biosis Biosis Citation Index (Web of Science)

1/3/16

FDA website http://www.fda.gov/ 1/3/16

NICE website http://www.nice.org.uk/ 1/3/16

AHRQ website http://www.ahrq.gov/ 1/3/16

CADTH website http://www.cadth.ca/ 1/3/16

ClinicalTrials.gov www.clinicaltrials.gov 1/3/16

World Health Organization International Clinical Trials Registry Platform (WHO ICTRP)

http://apps.who.int/trialsearch/

1/3/16

ISRCTTN registry (replaces previous Current Controlled Trials, including MRC Trials)

http://www.controlled-trials.com/

1/3/16

3

54

Database InterfaceDate searched

NHS EEDCochrane Library

25/2/16

Econlit Ovid 29/2/16

Cost-effectiveness analysis registry

https://research.tufts-nemc.org/cear4/1

29/2/16

1 The original search included a search of HEED. This database has now ceased publication.

4

55

56

1

Table S2. Number of records identified from each resource

DatabaseNumber of records downloaded

Number of unique records remaining for assessment after deduplication

MEDLINE and MEDLINE In-Process 2,845 2,257

EMBASE 7,250 923

Cochrane Database of Systematic Reviews (CDSR)

32 7

Cochrane Central Register of Controlled Trials (CENTRAL)

850 56

DARE Database of Abstracts of Reviews of Effects (DARE)

53 16

Health Technology Assessment Database (HTA)

67 21

Science Citation Index (SCI) and Conference Proceedings Citation Index – Science (CPCI-S)

6,107 566

Biosis 3,335 161

FDA website 5 5

NICE website 1 1

AHRQ website 0 0

CADTH website 8 5

ClinicalTrials.gov 624 383

World Health Organization International Clinical Trials Registry Platform (WHO ICTRP)

1,293 1,088

ISRCTN registry (replaces previous Current Controlled Trials, including MRC Trials)

35 23

NHS EED 47 5

Econlit 23 11

5

57

58

DatabaseNumber of records downloaded

Number of unique records remaining for assessment after deduplication

Cost-effectiveness analysis registry 125 14

American Association of Ophthalmology (AAO) congress abstracts

28 28

ARVO 205 2

EURETINA 14 14

Number of records found by checking trial records for associated publications

1 1

Total number of records 22,948 5,587

6

59

Table S3. Similarity of methods used in candidate trials considered for inclusion in the NMA of treatments for nAMD: Methods of

randomisation, allocation concealment, blinding, follow up and analysis methods

Study nameMethod of

randomisation and allocation

concealment

Blinding Follow up duration/ months

Number of drop outs – lost to follow up

ITT analysis and methods used to impute

missing dataPatient and personnel

Outcome assessment

ANCHOR (1) Not described. Yes Yes 24

Ranibizumab 0.3mg: 23 (16.4%);


PDT: 33 (23.1%).

ITT analysis was conducted on all

randomised patients. Complete case analysis was used to account for

missing data.

BeMOc (2) Not described. No No 54 weeksLoading dose arm: 0;

PRN arm: 1 (2%).

Analysis was carried out on the per-protocol

population; Complete case analysis was used to

account for missing data.

Biswas 2011 (3)

Randomisation list created using a random

number table;

Method of allocation concealment not

described.

Patients: Unclear;

Personnel: YesUnclear 18

Ranibizumab: 6 (10%);

Bevacizumab: 10 (16.7%).

Analysed as randomised. Complete case analysis was used to account for

missing data.

BRAMD (4) Not described. Unclear Unclear 12 Not reportedAuthors reported an ITT

approach was used, but no information is provided on

7

60

61

62

Study nameMethod of


concealment





Outcome assessment

how missing data were imputed.

CATT (5)

Patients randomly assigned in block;

Method of allocation concealment was not

described.

No No 24

Ranibizumab monthly: 12 (8.2%)

Bevacizumab monthly: 6 (4.4%);

Ranibizumab PRN: 23 (8%);

Bevacizumab PRN: 19 (7.0%);

Ranibizumab switched: 8 (5.8%);

Bevacizumab switched: 9 (6.9%).

Complete case analysis was used. Other methods were used in sensitivity analysis (analysis not

reported).

DETAIL (6)

Method of randomisation was not

reported; allocation was not concealed as this

was an open label trial.

No No 12 Unclear

It was unclear whether the ITT population was

analysed. It is unclear how missing data were

managed in the analysis.

ENS12 (7)

Randomisation list created using a

computer; allocation was not concealed as this was an open label

trial.

No Yes 12None. All patients

completed the 12-month follow-up


randomised patients. All patients completed the

study.

ENS5 (8) Method of No No 12 Bevacizumab 4 weeks: It was unclear whether the

8

Study nameMethod of


concealment





Outcome assessment

randomisation was not reported; allocation was

not concealed as this was an open label trial.

18 (28.1%);

Bevacizumab 6 weeks: 6 (9.5%);

Bevacizumab 8 weeks: 10 (15.6%).

ITT population was analysed. It is unclear how

missing data were managed in the analysis.

EXTEND-I (9)




No No 36

At 24 months


Ranibizumab 0.5mg: 9 (25%).


randomised patients. Complete case analysis

was used for missing data.

FOCUS (10) Not described.Patients: Yes;

Personnel: Some

Yes 24Ranibizumab: 9 (16.1%);

PDT: 15 (14.2%).


randomised patients. LOCF method was used

for missing data.

GEFAL 2013 (11) Not described. Yes Yes 12

Bevacizumab: 64 (25.1%);

Ranibizumab: 63 (25.6%).

Analysis carried out on per-protocol population. Complete case analysis

was used for missing data.

9

Study nameMethod of


concealment





Outcome assessment

Giustolisi 2011 (12)

Method of randomisation was not described; allocation was not concealed as this was an open-label

trial.

No Yes 6 None. All patients completed the study.


randomised patients. All patients completed the

study.

HARBOR (13)

Randomisation list created using a

computer; method of allocation concealment

was not reported clearly.

Yes Yes 24

Ranibizumab 0.5mg monthly: 18 (6.2%);

Ranibizumab 0.5mg PRN: 12 (4.4%);

Ranibizumab 2mg monthly: 16 (5.8%);

Ranibizumab 2mg PRN: 15 (5.5%).



for missing data.

IVAN (14)

Randomisation list created using computer and concealed via an

internet based system.

Yes Yes 24

Ranibizumab monthly: 23 (14.6%);

Bevacizumab monthly: 21 (14.2%);

Ranibizumab PRN: 18 (11.6%);

Bevacizumab PRN: 18 (12.4%).

Modified ITT analysis was conducted, based on the

requirement that a participant must have

received at least one dose of the allocated drug.

Complete case analysis was used for missing data.

Lebanon (15) Not described. No Yes 6Bevacizumab: 0;

PDT: 2 (6.25%).


analysed. Complete case analysis was used for

10

Study nameMethod of


concealment





Outcome assessment

missing data.

LUCAS (16)

Randomisation was computer generated

using fixed blocks and stratified by centre.

Method of allocation concealment was not

described.

Yes Yes 24

Bevacizumab (Year 1): 36 (16.4%*);

Bevacizumab (Year 2): 17 (24.1%);

Ranibizumab (Year 1): 34 (15.4%*);

Ranibizumab (Year 2): 15 (22.2%*).

Authors reported conducting an ITT, but only

213/220 (Bevacizumab) and 218/221

(Ranibizumab) patients were included in the

efficacy analysis.

MAAM (17)


reported; allocation was concealed via sealed

envelopes.

Patients: Yes; Personnel: No. Yes 6 Unclear


analysed. It is unclear how missing data were

managed in the analysis.

MANTA (18) Not described. Yes Yes 12

Bevacizumab: 33 (17.3%);

Ranibizumab: 36 (22.1%).



for missing data.

MARINA (19)

Randomisation list created using "dynamic

algorithm";

method of allocation concealment was not

reported.

Yes Yes 24 Unclear



for missing data.

11

Study nameMethod of


concealment





Outcome assessment

Moon 2011 (20)




No No 12 Unclear

Population analysed was not reported. The method

of dealing with missing data was not reported.

NCT01089517 (21) Not described. Unclear Unclear Not reported

Ranibizumab: 4 (2.7%*);

Pegpleranib (low dose) plus Ranibizumab: 5

(3.4%*);

Pegpleranib (high dose) plus Ranibizumab: 5

(3.3%*).

ITT analysis was conducted and missing

values were imputed using the LOCF method.

Subramanian 2010 (22)

Method of randomisation was not described; allocation

was concealed by pharmacist using identical syringes.

Yes Yes 12 Unclear

Population analysed was not reported. The method

of dealing with missing data was not reported.

TREX-AMD (23)

Unclear - patients were randomised

sequentially, but the randomisation process

was not described.

No No 12 Ranibizumab, monthly: 1 (5%*);

Ranibizumab,

Treat and extend: 6 (15%*).

Authors reported conducting an ITT, but only

19/20 (Ranibizumab, monthly) and 37/40

(Ranibizumab, TREX) patients were included in

ITT analysis.

Authors also report results for the per-protocol

12

Study nameMethod of


concealment





Outcome assessment

population.

VIEW I (24)

Randomisation list generated centrally using fixed blocks;


reported.

Yes Yes. 96 weeks

VIEW 1 and II combined

Ranibizumab: 90 (14.8%);

Aflibercept 2.0mg 4 weeks: 88 (14.3%);


Aflibercept 2.0mg 8 weeks: 103 (16.7%).


requirement that participant must have a baseline and one post baseline assessment.

LOCF method was used for missing data, although exceptions were applied.

VIEW II (24)

Randomisation list generated centrally using fixed blocks;


reported.

Yes Yes. 96 weeks

VIEW 1 and II combined

Ranibizumab: 90 (14.8%);



Aflibercept 2.0mg 8 weeks: 103 (16.7%).


requirement that participant must have a baseline and one post baseline assessment.

LOCF method was used for missing data, although exceptions were applied.

ITT- Intention to treat; LOCF – last observation carried forward; * - calculated percentages

13

6364

Table S4. Candidate trials and interventions assessed in the feasibility assessment of interventions for nAMD

ANCH

OR

BeM

Oc

Bisw

as

BRAM

D

CATT

DETA

IL

ENS-

12 (E

l-Mol

laye

ss 2

012)

ENS-

5 (L

ushc

hyk

2013

)

EXTE

ND-

1

FOCU

S

GEFA

L

Gius

tolis

i

HARB

OR

IVAN

Leba

non

LUCA

S IT

T

MAA

M

MAN

TA

MAR

INA

Moo

n 20

11

OPH

1001

Subr

aman

ian

TREX

-AM

D IT

T

VIEW

1

VIEW

1.5

VIEW

2

TOTA

L (a

ll st

udie

s)

AflibeceptA0.512xmon,PRN

301 613 296 1210A2.012xmon,PRN

304 597 309 1210A2.06x8-wkly,PRN

301 607 306 1214BevacizumabB1.0singledose+PEG0.36wklyPRN 17 17

B1.25 TREX213 213

B1.2512xmon,PRN 117 117B1.253x6weeks,PRN 50 50B1.253xmon,PRN 50 191 144 154 7 546B1.256wkly 57 13 70B1.258wkly 54 54B1.25fixmon 161 130 60 46 144 541B1.25PRN 49 251 60 360B2.5PRN

32 32PDTPDTPRN 143 56 30 229Pegaptanib

14

65

PEG0.3 6wklyPRN18 18

RanibizumabR 0.5 PRN 269 269R0.312xmon,PRN 35 35R0.33xmon,PRN N/A 0R0.36 xmon,Obs N/A 0R0.3fixmon 140 238 378R0.5 TREX

218 37 255R0.5+pegpleranib_fixmon

152 152R0.512xmon,PRN 127 41 304 595 291 1358R0.51xmon,PRN+vPDT1xmon,PRNfrommon3

17 17

R0.53xmon,PRN 54 N/A 183 30 275 154 163 N/A 15 874R0.56xmon,Obs N/A 0R0.5fixmon 139 166 134 275 155 240 N/A 148 19 1276R0.5fixmon+PDTPRN 105 105R2.03xmon,PRN 273 N/A 273R2.0fixmon 274 N/A 274ShamShamIVT

238 238

15

66

Table S5. List of studies included in the NMA*

Study name Reports

ANCHOR

Revicki DA, Rentz AM, Harnam N, Thomas VS, Lanzetta P. Reliability and Validity of the National Eye Institute Visual Function Questionnaire-25 in Patients with Age-Related Macular Degeneration. Investigative Ophthalmology & Visual Science 2010;51(2):712-717. Bressler NM, Chang TS, Suner IJ, Fine JT, Dolan CM, Ward J, et al. Vision-related function after ranibizumab treatment by better- or worse-seeing eye: clinical trial results from MARINA and ANCHOR. Ophthalmology 2010;117(4):747-56 e4. Suner IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: Validation studies from two phase 3 clinical trials. Investigative Ophthalmology and Visual Science 2009;50(8):3629-3635.Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355(14):1432-44.Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, et al. Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 2007;144(6):850-857. Bressler NM, Chang TS, Fine JT, Dolan CM, Ward J. Improved vision-related function after ranibizumab vs photodynamic therapy: a randomized clinical trial. Arch Ophthalmol 2009;127(1):13-21. Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology 2009;116(1):57-65 e5. Sadda SR, Stoller G, Boyer DS, Blodi BA, Shapiro H, Ianchulev T. Anatomical benefit from ranibizumab treatment of predominantly classic neovascular age-related macular degeneration in the 2-year ANCHOR study. Retina 2010;30(9):1390-1399.

16

67

68

Study name Reports

Biswas (2011)

Biswas P, Sengupta S, Choudhary R, Home S, Paul A, Sinha S. Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration. Indian J Ophthalmol 2011;59:191-6

CATT

CATT Research group, et al. Ranibizumab and Bevacizumab for treatment of neovascular age-related macular degeneration. Two year results. Ophthalmology 2012;119(7):1388-99DeCroos, F. C., et al. (2012). Optical coherence tomography grading reproducibility during the Comparison of Age-related Macular Degeneration Treatments Trials. Ophthalmology 119(12): 2549-2557.Catt Research Group. (2011). Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 364(20): 1897-1908.Grunwald, J. E., et al. (2012). Photographic assessment of baseline fundus morphologic features in the Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology 119(8): 1634-1641.Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, et al. Ranibizumab and Bevacizumab for Treatment of Neovascular Age-Related Macular Degeneration. Ophthalmology. 2012;119(7).

FOCUS

Heier JS, Boyer DS, Ciulla TA, Ferrone PJ, Jumper JM, Gentile RC, et al. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study. Arch Ophthalmol 2006;124(11):1532-42. Antoszyk AN, Tuomi L, Chung CY, Singh A. Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration (FOCUS): year 2 results. Am J Ophthalmol 2008;145(5):862-74. Apte RS, Alexander SL, Henry EC, Wong P, Tuomi L. An observational retrospective subgroup analysis of verteporfin photodynamic therapy-naive and previously treated patients in the focus trial. Retina 2011;31(1):56-64.

GEFAL (2013)Kodjikian L, Souied EH, Mimoun G, Mauget-Faysse M, Behar-Cohen F, Decullier E, et al. Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial. Ophthalmology. 2013;120(11):2300-9.

Giustolisi 2011

Giustolisi R, Fantozzi N, Staltari M, Marchiori J, Mastrangelo O, Marcucci R, et al. Combined intravitreal ranibizumab and verteporfin photodynamic therapy versus ranibizumab alone for the treatment of age-related macular

17

Study name Reportsdegeneration. Digital Journal of Ophthalmology 2011;17(3):23-30.

IVAN

Chakravarthy U, et al. Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial. Ophthalmology 2012 Jul;119(7):1399-411.Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet. 2013;382(9900):1258-67.

MANTA

Krebs I, Vecsei Marlovits V, Bodenstorfer J, Glittenberg C, Ansari Shahrezaei S, Ristl R, et al. Comparison of Ranibizumab monotherapy versus combination of Ranibizumab with photodynamic therapy with neovascular age-related macular degeneration. Acta Ophthalmol (Oxf). 2013;91(3):e178-83.Krebs I , Schmetterer L, Boltz A, Told R, Vecsei-Marlovits V, Egger S, et al. A randomised double-masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age-related macular degeneration. Br J Ophthalmol. 2013;97(3):266-71.

MARINA

Yue H, Kotlovker D, Shams N. A phase IIIb, multicenter, randomized, double-masked, sham injection−controlled study of the efficacy and safety of ranibizumab in subjects with subfoveal choroidal neovascularization (CNV) with or without classic CNV secondary to age-related macular degeneration. San Francisco: Genentech, Inc.; 2007. Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR. Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol 2007;125(11):1460-9.

Kaiser PK, Blodi BA, Shapiro H, Acharya NR, Group MS. Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114(10):1868-75.

Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR. Subgroup analysis of the MARINA study of ranibizumab in neovascular age-related macular degeneration. Ophthalmology 2007;114(2):246-52.

18

Study name ReportsBressler NM, Chang TS, Suner IJ, Fine JT, Dolan CM, Ward J, et al. Vision-related function after ranibizumab treatment by better- or worse-seeing eye: clinical trial results from MARINA and ANCHOR. Ophthalmology 2010;117(4):747-56 e4. Suner IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: Validation studies from two phase 3 clinical trials. Investigative Ophthalmology and Visual Science 2009;50(8):3629-3635.

Revicki DA, Rentz AM, Harnam N, Thomas VS, Lanzetta P. Reliability and Validity of the National Eye Institute Visual Function Questionnaire-25 in Patients with Age-Related Macular Degeneration. Investigative Ophthalmology & Visual Science 2010;51(2):712-717.

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-31.

OPH1001Ophthotech Corporation. A Safety and Efficacy Study of E10030 (Anti-PDGF Pegylated Aptamer) Plus Lucentis for Neovascular Age-Related Macular Degeneration. US: In: Clinicaltrials.gov [Internet], 2013.

Subramanian (2010)

Subramanian ML, Abedi G, Ness S, Ahmed E, Fenberg M, Daly MK, et al. Bevacizumab vs ranibizumab for age-related macular degeneration: 1-year outcomes of a prospective, double-masked randomised clinical trial. Eye. 2010;24(11):1708-15.

VIEW 1

Heier JS, VIEW 1 and VIEW 2 investigators. 96 weeks results from the VIEW 1 and VIEW 2 studies: Intravitreal aflibercept injection versus ranibizumab for neovascular AMD shows sustained improvements in visual acuity. ARVO 2012. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=14c6c603-88a2-46c6-8de1-ac24d9f71e9f&cKey=d2fd93bb-6f0e-4a1b-bdc0-b76e87b5b90a&mKey=%7bF0FCE029-9BF8-4E7C-B48E-9FF7711D4A0E%7d. Schmidt-Erfurth U, Heier JS, Majid A, Vitti R. Results of the phase 3 VIEW 1 and VIEW 2 studies of VEGF Trap-Eye vs. ranibizumab in nAMD. XXXIII International Congress of Ophthalmology 16-20th February 2012, Abu Dhabi, United Arab Emirates. Available at: http://www.woc2012.org/files/abstract_book_woc2012.pdf

19

Study name ReportsBayer Healthcare. Summary Report for the studies VIEW 1 and VIEW 2. Two randomized, double masked, active controlled, phase 3 studies of the efficacy, safety, and tolerability of repeated doses of intravitreal VEGF Trap-Eye in subjects with neovascular age-related macular degeneration (AMD). Bayer Healthcare; 2012. Regeneron Pharmaceuticals Inc. Clinical Summary Report: VIEW 1 study at 96 weeks. Regeneron Pharmaceuticals; 2012.Schmidt-Erfurth U, Heier JS, Majid A, Vitti R. Results of the phase 3 VIEW 1 and VIEW 2 studies of VEGF Trap-Eye vs. ranibizumab in nAMD. XXXIII International Congress of Ophthalmology 16-20th February 2012, Abu Dhabi, United Arab Emirates. Available at: http://www.woc2012.org/files/abstract_book_woc2012.pdf

HARBOR Busbee BG, Ho AC, Brown DM, Heier JS, Suner IJ, Li Z, et al. Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120(5):1046-56.

VIEW 2

Heier JS, VIEW 1 and VIEW 2 investigators. 96 weeks results from the VIEW 1 and VIEW 2 studies: Intravitreal aflibercept injection versus ranibizumab for neovascular AMD shows sustained improvements in visual acuity. ARVO 2012. Available at: http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=14c6c603-88a2-46c6-8de1-ac24d9f71e9f&cKey=d2fd93bb-6f0e-4a1b-bdc0-b76e87b5b90a&mKey=%7bF0FCE029-9BF8-4E7C-B48E-9FF7711D4A0E%7d. Schmidt-Erfurth U, Heier JS, Majid A, Vitti R. Results of the phase 3 VIEW 1 and VIEW 2 studies of VEGF Trap-Eye vs. ranibizumab in nAMD. XXXIII International Congress of Ophthalmology, 16-20th February 2012, Abu Dhabi, United Arab Emirates. Available at: http://www.woc2012.org/files/abstract_book_woc2012.pdf.

Bayer Healthcare. Summary Report for the studies VIEW 1 and VIEW 2. Two randomized, double masked, active controlled, phase 3 studies of the efficacy, safety, and tolerability of repeated doses of intravitreal VEGF Trap-Eye in subjects with neovascular age-related macular degeneration (AMD). Bayer Healthcare: 2012.

Bayer Healthcare. Clinical Study Report (2 years). VIEW 2. Report No.: A62515. Bayer Healthcare; 2012.

20

Study name ReportsRegeneron Pharmaceuticals Inc. Clinical Summary Report: VIEW 1 study at 52 weeks. Regeneron Pharmaceuticals: 2011.Bayer Healthcare. Integrated Study Protocol (VIEW 2): A randomized, double masked, active controlled, phase 3 study of the efficacy, safety, and tolerability of repeated doses of intravitreal VEGF Trap-Eye in subjects with neovascular age-related macular degeneration (AMD). Report No.: 311523. Bayer Healthcare; 2008.

Bayer Healthcare. Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) (VIEW 2). Bayer Healthcare; 2012.. Available from: http://clinicaltrials.gov/ct2/show/NCT00637377?term=VIEW&rank=7

Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-48.

EXTEND-1

Tano Y, et al. EXTEND-I: safety and efficacy of ranibizumab in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Acta Ophthalmol 2010;88(3):309-16.

Tano Y, Ohji M, Group E-IS. Long-term efficacy and safety of ranibizumab administered pro re nata in Japanese patients with neovascular age-related macular degeneration in the EXTEND-I study. Acta Ophthalmol. 2011;89(3):208-17.

Lebanon

Bashshur ZF, Schakal A, Hamam RN, El Haibi CP, Jaafar RF, Noureddin BN. Intravitreal bevacizumab vs verteporfin photodynamic therapy for neovascular age-related macular degeneration. Arch Ophthalmol 2007;125(10):1357-61.

Moon E, et al. 133/A268 Monthly versus PRN Ranibizumab for Neovascular AMD: A Randomized Phase 2 Open-Label Study. In: Fort Lauderdale: Association for Research in Vision and Ophthalmology; 2011: . NCT00764738. Study Investigating OCT, Multifocal ERG, and Microperimetry in Monthly Versus PRN Ranibizumab in Neovascular Age-Related Macular Degeneration. Torrance, CA: Retina Macula Institute; 2013.

ENS-12El-Mollayess GM, Mahfoud Z, Schakal AR, Salti HI, Jaafar D, Bashshur ZF. Fixed-Interval Versus OCT-Guided Variable Dosing of Intravitreal Bevacizumab in the Management of Neovascular Age-Related Macular Degeneration: A 12-

21

Study name ReportsMonth Randomized Prospective Study. Am J Ophthalmol. 2012;153(3):481-9.e1.

ENS-5Lushchyk, T., S. Amarakoon, et al. (2013). Bevacizumab in age-related macular degeneration: a randomized controlled trial on the effect of injections every 4weeks, 6weeks and 8weeks. Acta Opthalmologica 91(6): e456-461.

MAAM

Schmid-Kubista KE, Krebs I, Ansari-Shahrezaei S, Haas P, Hagen S, Binder S. Comparing treatment of neovascular age-related macular degeneration with sequential intravitreal Avastin and Macugen versus intravitreal mono-therapy--a pilot study. Curr Eye Res. 2011;36(10):958-63.Schmid-Kubista KE, Krebs I, Gruenberger B, Zeiler F, Schueller J, Binder S. Systemic bevacizumab (Avastin) therapy for exudative neovascular age-related macular degeneration. The BEAT-AMD-Study. Br J Ophthalmol. 2009;93(7):914-9.

BeMOcMenon G, Chandran M, Sivaprasad S, Chavan R, Narendran N, Yang Y. Is it necessary to use three mandatory loading doses when commencing therapy for neovascular age-related macular degeneration using bevacizumab? (BeMOc Trial). Eye (Lond). 2013;27(8):959-63..

LUCAS

Berg K, Hadzalic E, Gjertsen I, Forsaa V, Berger LH, Kinge B, et al. Ranibizumab or Bevacizumab for Neovascular Age-Related Macular Degeneration According to the Lucentis Compared to Avastin Study Treat-and-Extend Protocol: Two-Year Results. Ophthalmology. 2016;123(1):51-9.Berg K, Pedersen TR, Sandvik L, Bragadottir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015;122(1):146-52.

TREXWykoff CC, Croft DE, Brown DM, Wang R, Payne JF, Clark L, et al. Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: TREX-AMD 1-Year Results. Ophthalmology. 2015;122(12):2514-22.

*Two studies DETAIL and MOON did not report sufficient data for inclusion in the NMA

22

69

Table S6: A key to the trials and their corresponding IDs included in the network

diagram of mean change in VA of treatments for nAMD

Trial ID used in the network diagrams

ANCHOR A

BeMOc B

Biswas 2011 C

BRAMD D

CATT E

DETAIL F

ENS12 G

ENS5 H

EXTEND-I I

FOCUS J

GEFAL 2013 K

Giustolisi 2011 L

HARBOR M

IVAN N

Lebanon O

LUCAS P

MAAM Q

MANTA R

MARINA S

Moon 2011 T

NCT01089517 U

Subramanian 2010 V

TREX-AMD W

VIEW I X

VIEW II Y

23

70

71

24

72

Figure S2: A) Potential network available for mean change in visual acuity in treatments for nAMD at 0-3 months

25

73

B) Potential network available for mean change in visual acuity in treatments for nAMD at 4-12 months

26

74

75

C) Potential network available for mean change in visual acuity in treatments for nAMD at 13-24 months

27

76

77

Table S7: Assumptions regarding the equivalence of dosing regimens at 0–3 and 4–12 months for the networks of mean change in VA of

treatments for nAMD

Time frame Dosing regimen Assumed equivalent dosage

0 – 12 months

R 0.3 mg 12 x monthly, PRNRanibizumab 0.3mg fixed monthly

R 0.3 mg fixed monthlyR 0.5 12 x monthly, PRN

Ranibizumab 0.5mg fixed monthlyR 0.5 fixed monthly B 1.25 mg 12X monthly, PRN

Bevacizumab 1.25 monthlyB 1.25 fixed monthly

12 -24 months

R 0.3mg 12 x monthly, PRNRanibizumab 0.3mg fixed monthly

R 0.3 mg fixed monthlyR 0.5mg 12 x monthly, PRN

Ranibizumab 0.5mg fixed monthlyR 0.5 fixed monthlyB 1.25 mg 12X monthly, PRN

Bevacizumab 1.25 monthlyB 1.25 fixed monthly

PRN, pro re nata; T&E, treat and extend; R, ranibizumab; B, bevacizumab

28

78

79

8081

APPENDIX 1A: Full Search Strategies

This appendix includes the searches conducted for the Ranibizumab nAMD review in

August 2013 and also the searches conducted for this updated and expanded review

in February 2016.

29

82

83

84

85

86

A.1 MEDLINE

A.1.1. MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE (Ovid SP, 1946 to Present). Searched 27/08/13.

1 retinal degeneration/ or exp macular degeneration/ (24136)

2 Retinal Neovascularization/ (2317)

3 Choroidal Neovascularization/ (4602)

4 exp Macula Lutea/ (10124)

5 maculopath$.ti,ab. (2960)

6 ((macula$ or retina$ or sub-retina$ or choroid$) adj3 (degener$ or neovascula$

or neo-vascula$)).ti,ab. (24201)

7 (macula$ adj3 lutea).ti,ab. (111)

8 (AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV).ti,ab. (12194)

9 or/1-8 (49431)

10 Vascular Endothelial Growth Factor A/ai (6008)

11 Angiogenesis Inhibitors/ (19387)

12 Antibodies, Monoclonal, Humanized/ (31919)

13 Photosensitizing Agents/ (9783)

14 phototherapy/ or exp photochemotherapy/ (18575)

15 (aflibercept or eylea$ or zaltrap$ or trapeye$ or trap-eye$ or 862111-32-8 or

"862111328" or 8621-11-328 or 862111-328 or 862-111-328).ti,ab,rn. (343)

16 (ranibizumab or lucentis$ or rhufab$ or 347396-82-1 or "347396821" or

347396-821 or 347-396-821 or 3473-96-821).ti,ab,rn. (2067)

17 (bevacizumab or avastin$ or altuzan$ or 216974-75-3 or "216974753" or

216974-753 or 216-974-753 or 2169-74-753).ti,ab,rn. (13712)

18 (photodynamic$ or photo-dynamic$ or phototherap$ or photo-therap$ or

photosensiti$ or photo-sensiti$ or photochemotherap$ or photo-chemotherap$ or

pdt).ti,ab. (34872)

19 (verteporfin or visudyne$ or benzoporphyrin or porphyrin or 129497-78-5 or

"129497785" or 129497-785 or 129-497-785 or 1294-97-785).ti,ab,rn. (13646)

20 or/10-19 (98881)

30

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114

115

116

117

118

119

21 9 and 20 (6520)

22 animals/ not humans/ (3927983)

23 21 not 22 (6117)

A.1.2 MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE (Ovid SP, 1946 to Present). Searched 25/2/16

1 retinal degeneration/ or exp macular degeneration/ (25843)

2 Retinal Neovascularization/ (2346)

3 Choroidal Neovascularization/ (4331)

4 exp Macula Lutea/ (10610)

5 maculopath$.ti,ab,kf. (3309)


or neo-vascula$)).ti,ab,kf. (26136)

7 (macula$ adj3 lutea).ti,ab,kf. (400)

8 (AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV or

nAMD).ti,ab,kf. (13780)

9 or/1-8 (54123)

10 Vascular Endothelial Growth Factor A/ (38654)

11 angiogenesis inhibitors/ (18444)

12 antibodies, monoclonal, humanized/ (28873)

13 bevacizumab/ (7825)

14 ranibizumab/ (1920)

15 photosensitizing agents/ (11222)

16 phototherapy/ or exp photochemotherapy/ (20374)


"862111328" or 8621-11-328 or 862111-328 or 862-111-328).ti,ab,rn,kf. (714)


347396-821 or 347-396-821 or 3473-96-821).ti,ab,rn,kf. (2694)

19 (bevacizumab or avastin$ or 216974-75-3 or "216974753" or 216974-753 or

216-974-753 or 2169-74-753).ti,ab,rn,kf. (11929)

31

120

121

122

123

124

125

126

127

128

129

130

131

132

133

134

135

136

137

138

139

140

141

142

143

144

145

146

147

148

149

150

151



pdt).ti,ab,kf. (39844)

21 porphyrins/ (14851)


"129497785" or 129497-785 or 129-497-785 or 1294-97-785).ti,ab,rn,kf. (15453)

23 (fovista or E10030 or anti-PDGF or antiPDGF or anti-platelet derived growth

factor$1 or antiplatelet derived growth factor$1 or pegpleranib).ti,ab,rn,kf. (341)

24 or/10-23 (142433)

25 9 and 24 (7590)

26 exp animals/ not humans/ (4189142)

27 25 not 26 (6845)

A.2 EMBASE

A.2.1 Embase (OvidSP, 1974 to 2013 August 26). Searched 27/08/13

1 retina degeneration/ (8050)

2 exp retina macula degeneration/ (19251)

3 retina neovascularization/ (3595)

4 subretinal neovascularization/ (6459)

5 retina macula lutea/ (7341)






10 or/1-9 (52480)

11 angiogenesis inhibitor/ (13351)

12 monoclonal antibody/ (172618)

13 photosensitizing agent/ (8602)

14 phototherapy/ or photochemotherapy/ or photodynamic therapy/ (35430)

15 aflibercept/ (1181)

32

152

153

154

155

156

157

158

159

160

161

162

163

164

165

166

167

168

169

170

171

172

173

174

175

176

177

178

179

180

181

182

183

184

185


17 bevacizumab/ (28015)

18 verteporfin/ (1087)


347396-821 or 347-396-821 or 3473-96-821).ti,ab,rn. (3382)

20 (bevacizumab or avastin$ or altuzan$ or 216974-75-3 or "216974753" or

216974-753 or 216-974-753 or 2169-74-753).ti,ab,rn. (28743)



pdt).ti,ab. (42219)


"129497785" or 129497-785 or 129-497-785 or 1294-97-785).ti,ab,rn. (22130)


"862111328" or 8621-11-328 or 862111-328 or 862-111-328).ti,ab,rn. (1199)

24 or/11-23 (281116)

25 10 and 24 (6626)

26 (animal/ or animal experiment/ or animal model/ or nonhuman/) not exp human/

(5026682)

27 25 not 26 (6194)

A.2.2 Embase <1974 to 2016 February 24>. Searched 25/2/16

1 retina degeneration/ or exp macular degeneration/ (12225)

2 Retina Neovascularization/ (3921)

3 subretinal Neovascularization/ (7175)

4 retina Macula Lutea/ (7881)

5 maculopath$.ti,ab,kf. (3896)


or neo-vascula$)).ti,ab,kf. (30262)

7 (macula$ adj3 lutea).ti,ab,kf. (143)


nAMD).ti,ab,kf. (17667)

9 or/1-8 (55372)

10 Endothelial Cell Growth Factor/ (2079)

33

186

187

188

189

190

191

192

193

194

195

196

197

198

199

200

201

202

203

204

205

206

207

208

209

210

211

212

213

214

215

216

217

218

219

11 angiogenesis inhibitor/ (14865)

12 monoclonal antibody/ (183822)

13 bevacizumab/ or aflibercept/ or verteporfin/ or pegpleranib/ (40494)


15 photosensitizing agent/ (10247)

16 phototherapy/ or photochemotherapy/ or photodynamic therapy/ (41356)


"862111328" or 8621-11-328 or 862111-328 or 862-111-328).ti,ab,rn,kf. (2485)


347396-821 or 347-396-821 or 3473-96-821).ti,ab,rn,kf. (5280)

19 (bevacizumab or avastin$ or 216974-75-3 or "216974753" or 216974-753 or

216-974-753 or 2169-74-753).ti,ab,rn,kf. (39767)



pdt).ti,ab,kf. (48277)

21 porphyrin/ (14043)


"129497785" or 129497-785 or 129-497-785 or 1294-97-785).ti,ab,rn,kf. (23772)

23 (fovista or E10030 or anti-PDGF or antiPDGF or anti-platelet derived growth

factor$1 or antiplatelet derived growth factor$1 or pegpleranib).ti,ab,rn,kf. (378)

24 or/10-23 (316845)

25 9 and 24 (7250)

A.3 COCHRANE LIBRARY

Cochrane Database of Systematic Reviews: Issue 8 of 12, August 2013

Database of Abstracts of Reviews of Effects: Issue 3 of 4, July 2013

Cochrane Central Register of Controlled Trials: Issue 7 of 12, July 2013

Health Technology Assessment Database: Issue 3 of 4, July 2013

NHS Economic Evaluation Database: Issue 3 of 4, July 2013

#1 MeSH descriptor: [Retinal Degeneration] this term only 13

#2 MeSH descriptor: [Macular Degeneration] explode all trees 1033

34

220

221

222

223

224

225

226

227

228

229

230

231

232

233

234

235

236

237

238

239

240

241

242

243

244

245

246

247

248

249

250

251

252

253

#3 MeSH descriptor: [Retinal Neovascularization] this term only 40

#4 MeSH descriptor: [Choroidal Neovascularization] this term only 257

#5 MeSH descriptor: [Macula Lutea] explode all trees 270

#6 maculopath* 222

#7 ((macula* or retina* or "sub-retina*" or choroid*) adj3 (degener* or

neovascula* or "neo-vascula*")) 83

#8 (macula* adj3 lutea) 18

#9 AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV 1185

#10 (25-#9) 2163

#11 MeSH descriptor: [Vascular Endothelial Growth Factor A] this term only and

with qualifiers: [Antagonists & inhibitors - AI] 179

#12 MeSH descriptor: [Angiogenesis Inhibitors] this term only 477

#13 MeSH descriptor: [Antibodies, Monoclonal, Humanized] this term only

1542

#14 MeSH descriptor: [Photosensitizing Agents] this term only 365

#15 MeSH descriptor: [Phototherapy] this term only 575

#16 MeSH descriptor: [Photochemotherapy] explode all trees 533

#17 aflibercept or eylea* or zaltrap* or trapeye* or "trap-eye*" or "862111-32-8" or

"862111328" or "8621-11-328" or "862111-328" or "862-111-328" 29

#18 ranibizumab or lucentis* or rhufab* or "347396-82-1" or "347396821" or

"347396-821" or "347-396-821" or "3473-96-821" 234

#19 bevacizumab or avastin* or altuzan* or "216974-75-3" or "216974753" or

"216974-753" or "216-974-753" or "2169-74-753" 781

#20 photodynamic* or "photo-dynamic*" or phototherap* or "photo-therap*" or

"photosensiti*" or "photo-sensiti*" or photochemotherap* or "photo-chemotherap*" or

pdt 2889

#21 verteporfin or visudyne* or benzoporphyrin or porphyrin or "129497-78-5" or

"129497785" or "129497-785" or "129-497-785" or "1294-97-785" 342

#22 (13-#21) 5047

#23 #10 and #22 608

#24 #23 in Cochrane Reviews (Reviews and Protocols) 30

#25 #23 in Other Reviews 22

#26 #23 in Trials 473

#27 #23 in Technology Assessments 45

35

254

255

256

257

258

259

260

261

262

263

264

265

266

267

268

269

270

271

272

273

274

275

276

277

278

279

280

281

282

283

284

285

286

287

#28 #23 in Economic Evaluations 37

Cochrane Library (Wiley InterScience) Searched 25/2/16

Cochrane Database of Systematic Reviews : Issue 2 of 12, February 2016

Database of Abstracts of Reviews of Effect : Issue 2 of 4, April 2015

Cochrane Central Register of Controlled Trials : Issue 1 of 12, January 2016

Health Technology Assessment Database : Issue 1 of 4, January 2016

NHS Economic Evaluation Database: : Issue 2 of 4, April 2015

#1 MeSH descriptor: [Retinal Degeneration] this term only 18

#2 MeSH descriptor: [Macular Degeneration] explode all trees 1441

#3 MeSH descriptor: [Retinal Neovascularization] this term only 55

#4 MeSH descriptor: [Choroidal Neovascularization] this term only 298

#5 MeSH descriptor: [Macula Lutea] explode all trees 325

#6 maculopath* 297

#7 ((macula* or retina* or "sub-retina*" or choroid*) near (degener* or

neovascula* or "neo-vascula*")) 2092

#8 (macula* near lutea) 305

#9 (AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV or nAMD)

1513

#10 (26-#9) 3349

#11 MeSH descriptor: [Vascular Endothelial Growth Factor A] this term only

852

#12 MeSH descriptor: [Angiogenesis Inhibitors] this term only 856

#13 MeSH descriptor: [Antibodies, Monoclonal, Humanized] this term only

2894

#14 MeSH descriptor: [Bevacizumab] this term only 563

#15 MeSH descriptor: [Ranibizumab] this term only 252

#16 MeSH descriptor: [Photosensitizing Agents] this term only 538

#17 MeSH descriptor: [Phototherapy] this term only 704

#18 MeSH descriptor: [Photochemotherapy] explode all trees 728

#19 aflibercept or eylea* or zaltrap* or trapeye* or "trap-eye*" or "862111-32-8" or

"862111328" or "8621-11-328" or "862111-328" or "862-111-328" 146

36

288

289

290

291

292

293

294

295

296

297

298

299

300

301

302

303

304

305

306

307

308

309

310

311

312

313

314

315

316

317

318

319

320

321

#20 ranibizumab or lucentis* or rhufab* or "347396-82-1" or "347396821" or

"347396-821" or "347-396-821" or "3473-96-821" 594

#21 bevacizumab or avastin* or altuzan* or "216974-75-3" or "216974753" or

"216974-753" or "216-974-753" or "2169-74-753" 2005

#22 photodynamic* or "photo-dynamic*" or phototherap* or "photo-therap*" or

"photosensiti*" or "photo-sensiti*" or photochemotherap* or "photo-chemotherap*" or

pdt 3981

#23 verteporfin or visudyne* or benzoporphyrin or porphyrin or "129497-78-5" or

"129497785" or "129497-785" or "129-497-785" or "1294-97-785" 363

#24 MeSH descriptor: [Porphyrins] this term only 149

#25 fovista or E10030 or anti-PDGF or antiPDGF or "anti-platelet derived growth

factor*" or "antiplatelet derived growth factor*" or pegpleranib 6

#26 (27-#25) 9044

Cochrane Database of Systematic Reviews: 32 records

Database of Abstracts of Reviews of Effect: 53 records

Cochrane Central Register of Controlled Trials: 850 records

Health Technology Assessment Database: 67 records

NHS Economic Evaluation Database: 47 records

A.4 SCIENCE CITATION INDEX EXPANDED

A.4.1 Science Citation Index Expanded (Web of Science, Thompson Reuters; 1900- 2013-08-23). Searched 27/08/13

Databases=SCI-EXPANDED IC Timespan=All years

# 12 4,501 #11 AND #5

# 11 99,234 #10 OR #9 OR #8 OR #7 OR #6

# 10 33,729 TS=("verteporfin" or "visudyne*" or "benzoporphyrin" or

"porphyrin" or "129497-78-5" or "129497785" or "129497-785" or "129-497-785" or

"1294-97-785")

37

322

323

324

325

326

327

328

329

330

331

332

333

334

335

336

337

338

339

340

341

342

343

344

345

346

347

348

349

350

351

352

353

354

# 9 59,399 TS=("photodynamic*" or "photo-dynamic*" or "phototherap*" or

"photo-therap*" or "photosensiti*" or "photo-sensiti*" or "photochemotherap*" or

"photo-chemotherap*" or "pdt")

# 8 11,565 TS=("bevacizumab" or "avastin*" or "altuzan*" or "216974-75-3"

or "216974753" or "216974-753" or "216-974-753" or "2169-74-753")

# 7 1,921 TS=("ranibizumab" or "lucentis*" or "rhufab*" or "347396-82-1" or

"347396821" or "347396-821" or "347-396-821" or "3473-96-821")

# 6 229 TS=("aflibercept" or "eylea*" or "zaltrap*" or "trapeye*" or "trap-eye*" or

"862111-32-8" or "862111328" or "8621-11-328" or "862111-328" or "862-111-328")

# 5 35,088 #4 OR #3 OR #2 OR #1

# 4 11,868 TS=("AMD" or "wAMD" or "GAMD" or "ARMD" or "wARMD" or

"CNV" or "mCNV")

# 3 76 TS=("macula*" NEAR/3 "lutea")

# 2 26,909 TS=(("macula*" or "retina*" or "sub-retina*" or "choroid*")

NEAR/3 ("degener*" or "neovascula*" or "neo-vascula*"))

# 1 4,722 TS="maculopath*"

A.4.2 Conference Proceedings Citation Index- Science (Web of Science, Thompson Reuters; 1990- 2013-08-23). Searched 28/08/13

Databases=CPCI-S Timespan=All years

# 12 519 #11 AND #5

# 11 14,434 #10 OR #9 OR #8 OR #7 OR #6

# 10 2,886 TS=("verteporfin" or "visudyne*" or "benzoporphyrin" or "porphyrin" or

"129497-78-5" or "129497785" or "129497-785" or "129-497-785" or "1294-97-785")




# 8 1,935 TS=("bevacizumab" or "avastin*" or "altuzan*" or "216974-75-3" or

"216974753" or "216974-753" or "216-974-753" or "2169-74-753")

# 7 84 TS=("ranibizumab" or "lucentis*" or "rhufab*" or "347396-82-1" or

"347396821" or "347396-821" or "347-396-821" or "3473-96-821")


"862111-32-8" or "862111328" or "8621-11-328" or "862111-328" or "862-111-328")

38

355

356

357

358

359

360

361

362

363

364

365

366

367

368

369

370

371

372

373

374

375

376

377

378

379

380

381

382

383

384

385

386

387

388

# 5 5,130 #4 OR #3 OR #2 OR #1

# 4 2,286 TS=("AMD" or "wAMD" or "GAMD" or "ARMD" or "wARMD" or "CNV"

or "mCNV")


# 2 3,289 TS=(("macula*" or "retina*" or "sub-retina*" or "choroid*") NEAR/3

("degener*" or "neovascula*" or "neo-vascula*"))

# 1 545 TS="maculopath*"

A.4.3 Science Citation Index Expanded (Web of Science, Thompson Reuters; 1900- 2016-02-24). Searched 25/2/16

Conference Proceedings Citation Index- Science (Web of Science, Thompson

Reuters; 1990- 2016-02-24). Searched 25/2/16

Databases=CPCI-S Timespan=All years

Databases=SCI-EXPANDED IC Timespan=All years

# 13 6,107 #12 AND #5

# 12 129,285 #11 OR #10 OR #9 OR #8 OR #7 OR #6

# 11 288 TS=(“fovista” or “E10030” or “anti-PDGF” or “antiPDGF” or "anti-

platelet derived growth factor*" or "antiplatelet derived growth factor*" or

“pegpleranib”)



"1294-97-785")




# 8 17,979 TS=("bevacizumab" or "avastin*" or "altuzan*" or "216974-75-3"

or "216974753" or "216974-753" or "216-974-753" or "2169-74-753")


"347396821" or "347396-821" or "347-396-821" or "3473-96-821")

39

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http://apps.webofknowledge.com/summary.do?product=WOS&doc=1&qid=9&SID=Z1FdZgKq5pLgXkdQorx&search_mode=AdvancedSearch&update_back2search_link_param=yes





http://apps.webofknowledge.com/summary.do?product=WOS&doc=1&qid=14&SID=Z1FdZgKq5pLgXkdQorx&search_mode=CombineSearches&update_back2search_link_param=yes



"862111-32-8" or "862111328" or "8621-11-328" or "862111-328" or "862-111-328")

# 5 46,057 #4 OR #3 OR #2 OR #1

Indexes=SCI-EXPANDED, CPCI-S Timespan=All years


"CNV" or "mCNV" or "nAMD")





40

421

422

423

424

425

426

427

428

429

430

431

432







A.5 BIOSIS

A.5.1 BIOSIS Citation Index- Science (Web of Knowledge, Thompson Reuters; 1969- 2013-08-23). Searched 28/08/13

# 12 2,596 #11 AND #5

# 11 51,980 #10 OR #9 OR #8 OR #7 OR #6


"862111-32-8" or "862111328" or "8621-11-328" or "862111-328" or "862-111-328")



"1294-97-785")





"216974753" or "216974-753" or "216-974-753" or "2169-74-753")


"347396821" or "347396-821" or "347-396-821" or "3473-96-821")

# 5 31,702 #4 OR #3 OR #2 OR #1


"CNV" or "mCNV")





A.5.2 BIOSIS Citation Index (Web of Science, Thompson Reuters; 1969- 2016-02-29). Searched 1/3/16

Indexes=BCI Timespan=All years

# 13 3,335 #12 AND #5

41

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434

435

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437

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441

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http://apps.webofknowledge.com/summary.do?product=BCI&doc=1&qid=13&SID=U1wh4oGw4mnk67oMe5M&search_mode=CombineSearches&update_back2search_link_param=yes

# 12 60,362 #11 OR #10 OR #9 OR #8 OR #7 OR #6

# 11 368 TS=(“fovista” or “E10030” or “anti-PDGF” or “antiPDGF” or "anti-

platelet derived growth factor*" or "antiplatelet derived growth factor*" or

“pegpleranib”)


"862111-32-8" or "862111328" or "8621-11-328" or "862111-328" or "862-111-328")



"1294-97-785")





"216974753" or "216974-753" or "216-974-753" or "2169-74-753")


"347396821" or "347396-821" or "347-396-821" or "3473-96-821")

# 5 37,967 #4 OR #3 OR #2 OR #1


"CNV" or "mCNV" or "nAMD")





A.6 ECONLIT

A.6.1 Econlit (OvidSP, 1961 to July 2013). Searched 28/08/13


42

466

467

468

469

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471

472

473

474

475

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477

478

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482

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http://apps.webofknowledge.com/summary.do?product=BCI&doc=1&qid=1&SID=U1wh4oGw4mnk67oMe5M&search_mode=AdvancedSearch&update_back2search_link_param=yes
















5 1 or 2 or 3 or 4 (18)

A.6.2 Econlit (OvidSP, 1961 to Jan 2016). Searched 28/02/16






nAMD).ti,ab. (22)

5 or/1-4 (23)

A.7 CEA REGISTRY

A.7.1 CEA Registry (https://research.tufts-nemc.org/cear4/Home.aspx) Searched 28/08/13

maculopathy – 0 results

macular degeneration – 29 results (2 added to EndNote, 27 duplicates)

retinal degeneration – 0 results

retinal neovascularisation – 0 results

retinal neovascularization – 0 results

macula lutea – 0 results

choroidal neovascularization - 14 results (1 added to EndNote, 13 duplicates)

choroidal neovascularisation - 2 results (0 added to EndNote, 2 duplicates)

A.7.2 CEA Registry (https://research.tufts-nemc.org/cear4/) Searched 29/2/16

43

496

497

498

499

500

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523

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525

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527

528

529

maculopathy – 1 result

macular – 46 results

retinal – 15 results

macula– 46 results (same as macular)

choroidal – 17 results

A.8 HEED

A.8.1 HEED (Wiley InterScience) Searched 28/08/13

AX=maculopath* 3

AX='macular degeneration' within 3 87

AX='retinal degeneration' within 3 0

AX='macula lutea' within 3 0

AX='choroidal neovascularization' within 3 15

AX='choroidal neovascularisation' within 3 6

AX='retinal neovascularization' within 3 1

AX='retinal neovascularisation' within 3 1

AX=AMD or wAMD or GAMD or ARMD or wARMD or CNV or mCNV 61

CS=1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 119

A.8.2 HEED (Wiley InterScience) Update search

This database is no longer available to search.

A.9 FDA WEBSITE

A.9.1 FDA website (http://www.fda.gov/) Searched 02/09/13

44

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Searched the following terms separately using the drugs @ FDA search box

[http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm]:

lucentis

avastin

eylea

verteporfin

Results were scanned and 18 relevant records were downloaded.

45

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562

563

564

565

566

567

568

569

570

A.9.2 FDA website (http://www.fda.gov/) Searched 1/3/2016

Searched the following terms separately using the drugs @ FDA search box

[http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm] and limiting to

documents with dates since 02/09/2013 (last search date).

Fovista – 0 records

Pegpleranib – 0 records

Lucentis

3 label changes since 2013

Final current label downloaded

Avastin



Summary review for regulatory action downloaded

Eylea (aflibercept)



ZIV-aflibercept – 2 label changes


Verteporfin

2 label changes since 2013 but no new label issued

A.10 NICE WEBSITE

A.10.1 NICE website Searched 03/09/13

Searched the following terms separately using the NICE site search engine

[http://www.nice.org.uk/]

age-related macular degeneration - results filtered to ‘guidance’

46

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572

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Following results filtered to ‘guidance’ and ‘eye diseases’

lucentis

ranibizumab

rhufab

avastin

bevacizumab

altuzan

eylea

aflibercept

trap-eye

trapeye

zaltrap

verteporfin

visudyne

benzoporphyrin

porphyrin


A.10.2 NICE website Searched 1/3/16

Searched the following terms separately using the NICE site search engine

[http://www.nice.org.uk/]

age-related macular degeneration - results filtered to ‘guidance’. 57 results.

The only downloaded results were those since Sept 2013:

epiretinal brachytherapy – downloaded guidance

pegaptanib – not recommended – no report to download

47

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604

605

606

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618

619

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621

622

623

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627

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631

The results from the following search were filtered to those records in the last three

years:

fovista OR pegpleranib OR lucentis OR ranibizumab OR rhufab OR avastin

OR bevacizumab OR altuzan OR eylea OR aflibercept OR trap-eye OR

tapeye OR zaltrap OR verteporfin OR visudyne OR benzoporphyrin OR

porphyrin

Results were scanned and 0 new relevant records were downloaded.

A.11 AHRQ

A.11.1 AHRQ website Searched 04/09/13

Searched the following terms separately using the AHRQ site search engine

[http://www.ahrq.gov/index.html]

macular degeneration [in title of page]

lucentis

ranibizumab

rhufab

avastin

bevacizumab macular [search with all of the words]

altuzan

eylea

aflibercept

trap-eye

trapeye

48

632

633

634

635

636

637

638

639

640

641

642

643

644

645

646

647

648

649

650

651

652

653

654

655

656

657

658

659

660

661

zaltrap

verteporfin

visudyne

benzoporphyrin

porphyrin


49

662

663

664

665

666

667

668

669

A.11.2 AHRQ website Searched 04/09/13

Searched the following terms separately using the AHRQ site search engine

[http://www.ahrq.gov/index.html]:

macular degeneration [exact phrase, in title of page]

returns NICE guidance Jul 2013 – not downloaded

fovista pegpleranib lucentis ranibizumab rhufab avastin bevacizumab altuzan

eylea aflibercept trap-eye trapeye zaltrap verteporfin visudyne benzoporphyrin

porphyrin [any word, anythwhere in the document]

Results were scanned and 0 additional relevant records were

downloaded.

A.12 CADTH WEBSITE

A.12.1 CADTH website Searched 04/09/13

Searched the following terms separately using the CADTH site search engine

[http://www.cadth.ca/en]:

macular degeneration

lucentis

ranibizumab

rhufab

avastin

bevacizumab

altuzan

eylea

aflibercept

"trap-eye"

50

670

671

672

673

674

675

676

677

678

679

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681

682

683

684

685

686

687

688

689

690

691

692

693

694

695

696

697

698

699

trapeye

zaltrap

verteporfin

visudyne

benzoporphyrin

porphyrin


A.12.2 CADTH website Searched 1/3/16

Searched the following terms separately using the CADTH site search engine

[http://www.cadth.ca] and looked for publications since Sept 2013:


downloaded a review on aflibercept

downloaded a review of bevacizumab

downloaded a review of lucentis

downloaded five documents for common drug review of aflibercept

Records were assessed for relevance by an information specialist; five relevant, non

duplicate records were loaded into Endnote.

A.13 CLINICALTRIALS.GOV

A.13.1 ClinicalTrials.gov Searched 04/09/13

The following 3 searches were run separately using ‘Targeted Search’.

Search 1:

51

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715

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718

719

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730

Condition field: wet OR "macular degeneration" OR choroidal OR "macula lutea" OR

"retinal degeneration" OR "retina degeneration" OR AMD OR wAMD OR GAMD OR

ARMD OR wARMD OR CNV OR mCNV OR maculopathy OR maculopathies

Intervention field: lucentis OR ranibizumab OR rhufab OR avastin OR bevacizumab

OR altuzan OR eylea OR aflibercept OR trap-eye OR "trap eye" OR trapeye OR

zaltrap OR verteporfin OR visudyne OR benzoporphyrin OR porphyrin

Results = 420

Search 2:




Intervention field: photo OR phototherapy OR "photo-therapy" OR phototherapies

OR "photo-therapies" OR photodynamic OR "photo-dynamic" OR

photochemotherapy OR "photo-chemotherapy" OR photochemotherapies OR

"photo-chemotherapies" OR photosensitive OR "photo-sensitive"

Results = 83

Search 3:




52

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732

733

734

735

736

737

738

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743

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745

746

747

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749

750

751

752

753

754

755

756

757

758

759

Intervention field: pdt

Results = 69

53

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761

762

763

A.13.2 ClinicalTrials.gov Searched 01/03/16

The following 3 searches were run separately using ‘Targeted Search’ in the

Advanced search option.

Search 1:




Intervention field: fovista OR pegpleranib OR lucentis OR ranibizumab OR rhufab

OR avastin OR bevacizumab OR altuzan OR eylea OR aflibercept OR trap-eye OR

"trap eye" OR trapeye OR zaltrap OR verteporfin OR visudyne OR benzoporphyrin

OR porphyrin

Results

Records added since 03/09/2013: 192 records

Records updated since 03/09/2013: 369 records

Search 2:




Intervention field: photo OR phototherapy OR "photo-therapy" OR phototherapies

OR "photo-therapies" OR photodynamic OR "photo-dynamic" OR

photochemotherapy OR "photo-chemotherapy" OR photochemotherapies OR

"photo-chemotherapies" OR photosensitive OR "photo-sensitive"

Results



54

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784

785

786

787

788

789

790

791

792

793

794

795

796

797

Search 3:




Intervention field: pdt

Results



55

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799

800

801

802

803

804

805

806

807

808

809

810

A.14 WORLD HEALTH ORGANIZATION INTERNATIONAL CLINICAL TRIALS REGISTRY PLATFORM (WHO ICTRP)

A.14.1 World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) Searched 04/09/13

Searched following using interface at: http://apps.who.int/trialsearch/

macular degeneration OR choroidal neovasc* OR choroidal neo-vasc* OR macula

lutea OR retina degeneration OR retinal degeneration OR AMD OR wAMD OR

GAMD OR ARMD OR wARMD OR CNV OR mCNV OR maculopath* = 904 trials

A.14.2 World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) Searched 01/03/2016

Searched following using interface at: http://apps.who.int/trialsearch/

macular degeneration OR choroidal neovasc* OR choroidal neo-vasc* OR macula

lutea OR retina degeneration OR retinal degeneration OR AMD OR wAMD OR

GAMD OR ARMD OR wARMD OR CNV OR mCNV OR maculopath*

1655 records for 1293 trials (1293 downloaded)

A.15 CURRENT CONTROLLED TRIALS/ ISRCTTN

A.15.1 Current Controlled Trials Searched 06/09/13

Searched International Standard Randomised Controlled Trial Number Register

[http://www.controlled-trials.com/isrctn/] using following terms:

56

811

812

813

814

815

816

817

818

819

820

821

822

823

824

825

826

827

828

829

830

831

832

833

834

835

836

837

838

839

840

841

macular degeneration OR choroidal OR macula lutea OR retina degeneration OR

retinal degeneration OR AMD OR wAMD OR GAMD OR ARMD OR wARMD OR

CNV OR mCNV OR maculopathy OR maculopathies = 75 results

Searched metaRegister of Controlled Trials (mRCT) [http://www.controlled-

trials.com/mrct/] - all registers selected apart from the NIH ClinicalTrials.gov Register

using following terms:

macular degeneration OR choroidal OR macula lutea OR retina degeneration OR

retinal degeneration OR AMD OR wAMD OR GAMD OR ARMD OR wARMD OR

CNV OR mCNV OR maculopathy OR maculopathies = 83 results

A.15.2 Searched International Standard Randomised Controlled Trial Number Register Searched 1/3/16 This register is the current content of Controlled Clinical Trials [http://www.controlled-

trials.com/isrctn/].

It was searched using the following terms:

“macular degeneration” OR choroidal OR “macula lutea” OR “retina degeneration”

OR “retinal degeneration” OR AMD OR wAMD OR GAMD OR ARMD OR wARMD

OR CNV OR mCNV OR maculopathy OR maculopathies OR nAMD

35 results – downloaded to a word document with links

A.16 AMERICAN ASSOCIATION OF OPHTHALMOLOGY (AAO) CONGRESS ABSTRACTS

A.16.1 American Association of Ophthalmology (AAO) congress abstracts Searched 06/09/13

57

842

843

844

845

846

847

848

849

850

851

852

853

854

855

856

857

858

859

860

861

862

863

864

865

866

867

868

869

870

871

872

873

Searched using the Program Search and Meeting Archive

[https://secure.aao.org/apps/MeetingArchive/tabid/433/Default.aspx], limited to years

2009 - 2013 using the following terms.

Lucentis = 14

Ranibizumab = 110

Rhufab = 4

Avastin = 27

Bevacizumab = 144

Altuzan = 4

Eylea = 5

Aflibercept = 11

trap-eye = 15

trapeye = 4

zaltrap = 4

verteporfin = 11

visudyne = 4

benzoporphyrin = 4

porphyrin = 4

photodynamic = 28

pdt = 21

phototherap = 13

photochemo = 4

photo-=4

435 results were downloaded.

58

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875

876

877

878

879

880

881

882

883

884

885

886

887

888

889

890

891

892

893

894

895

896

897

898

899

900

A.16.2 American Association of Ophthalmology (AAO) congress abstracts Searched 1/3/16

Searched scientific posters at http://aao.scientificposters.com/epsSearchAAO.cfm

limited to 2014 and 2015:

Any type of study design

Search term: fovista

Search term: pegpleranib

RCTs only (downloaded records)

Lucentis

Ranibizumab

Rhufab

Avastin

Bevacizumab

Altuzan

Eylea

Aflibercept

trap-eye

trapeye

zaltrap

verteporfin

visudyne

benzoporphyrin

porphyrin

photodynamic

pdt

phototherapy

photochemotherapy

28 records were downloaded.

59

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902

903

904

905

906

907

908

909

910

911

912

913

914

915

916

917

918

919

920

921

922

923

924

925

926

927

928

929

930

931

932

933

934

http://aao.scientificposters.com/epsSearchAAO.cfm

A.17 ASSOCIATION FOR RESEARCH IN VISION AND OPHTHALMOLOGY (ARVO) CONGRESS ABSTRACTS

A.17.1 Association for Research in Vision and Ophthalmology (ARVO) congress abstracts Searched 08/09/13

Searched via the Investigative Ophthalmology & Visual Science (IOVS) database

(holds all ARVO Annual Meeting Abstracts and all IOVS article abstracts, from

February 1962 to the present): [http://www.iovs.org/search.dtl?arvomtgsearch=true]

Searched following in text, abstract, title field; search limited to ARVO Meeting

Abstracts, dates between Jan 2009 and Dec 2013.

("macular degeneration" OR "choroidal neovasc*" OR "choroidal neo-vasc*" OR

"macula lutea" OR "retinal degeneration" OR "retina degeneration" OR AMD OR

wAMD OR GAMD OR ARMD OR wARMD OR CNV OR mCNV OR maculopath*)

AND (lucentis OR ranibizumab OR rhufab OR avastin OR bevacizumab OR altuzan

OR eylea OR aflibercept OR trap-eye OR "trap eye" OR trapeye OR zaltrap OR

verteporfin OR visudyne OR benzoporphyrin OR porphyrin OR photodynamic OR

pdt) = 930 results

("macular degeneration" OR "choroidal neovasc*" OR "choroidal neo-vasc*" OR

"macula lutea" OR "retinal degeneration" OR "retina degeneration" OR AMD OR

wAMD OR GAMD OR ARMD OR wARMD OR CNV OR mCNV OR maculopath*)

AND ("photo-dynamic*" OR photochemo* OR "photo-chemo*" OR phototherap* OR

"photo-therap*") = 1 result (dup of result retrieved in above set – not downloaded]

A.17.2 Association for Research in Vision and Ophthalmology (ARVO) congress abstracts (1/3/16)

60

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936

937

938

939

940

941

942

943

944

945

946

947

948

949

950

951

952

953

954

955

956

957

958

959

960

961

962

963

964

965

These abstracts are indexed in the databases searched as part of the Web of

Science resources. We carried out an additional search on ALL databases (Web of

science core collection, Biosis citation index, Korean Journal database, medline,

scielo citation index) as follows:

TOPIC: (fovista or E10030 or anti-PDGF or antiPDGF or "anti-platelet derived growth

factor*" or "antiplatelet derived growth factor*" or pegpleranib OR "aflibercept" or

"eylea*" or "zaltrap*" or "trapeye*" or "trap-eye*" or "862111-32-8" or "862111328" or

"8621-11-328" or "862111-328" or "862-111-328 OR "verteporfin" or "visudyne*" or

"benzoporphyrin" or "porphyrin" or "129497-78-5" or "129497785" or "129497-785" or

"129-497-785" or "1294-97-785" OR photodynamic*" or "photo-dynamic*" or

"phototherap*" or "photo-therap*" or "photosensiti*" or "photo-sensiti*" or

"photochemotherap*" or "photo-chemotherap*" or "pdt" OR "bevacizumab" or

"avastin*" or "altuzan*" or "216974-75-3" or "216974753" or "216974-753" or "216-

974-753" or "2169-74-753" OR "ranibizumab" or "lucentis*" or "rhufab*" or "347396-

82-1" or "347396821" or "347396-821" or "347-396-821" or "3473-96-

821") ANDTOPIC: ("AMD" or "wAMD" or "GAMD" or "ARMD" or "wARMD" or "CNV"

or "mCNV" or "nAMD" OR "macula* lutea" OR (("macula*" or "retina*" or "sub-

retina*" or "choroid*") NEAR/3 ("degener*" or "neovascula*" or "neo-vascula*")) OR

maculopathy*)AND PUBLICATION NAME: (IOVS)

Timespan: 2013-2016.

Search language=Auto


A.18 EUROPEAN SOCIETY OF RETINA SPECIALISTS (EURETINA) CONGRESS ABSTRACTS

A.18.1 European Society of Retina Specialists (EURETINA) congress abstracts Searched 08/09/13

61

966

967

968

969

970

971

972

973

974

975

976

977

978

979

980

981

982

983

984

985

986

987

988

989

990

991

992

993

994

995

996

997

Searched via the EURETINA Abstracts Archive

[http://www.euretina.org/abstracts.asp]

Search functionality limited. Searched following terms in Paper Title:


choroidal neovascularization

choroidal neovascularisation

macula lutea

retina degeneration

retinal degeneration

AMD

wAMD

GAMD

ARMD

wARMD

CNV

mCNV

maculopathy

maculopathies

347 results were downloaded.

A.18.2 European Society of Retina Specialists (EURETINA) congress abstracts for 2014 and 2015. Searched 1/3/16

Searched via the EURETINA Abstracts Archive

[http://www.euretina.org/abstracts.asp]

62

998

999

1000

1001

1002

1003

1004

1005

1006

1007

1008

1009

1010

1011

1012

1013

1014

1015

1016

1017

1018

1019

1020

1021

1022

1023

1024

1025

Search options were not operational.

Browsed presentation type ‘Free paper’ and within that category browsed sessions:

AMD1

AMD2

New drug treatment

Quick fire free papers sessions 1 to 5

Browsed presentation type ‘Poster’ and within that category browsed session on

AMD.


15th Euretina conference (2015)

Browsed ‘Free papers’ and within that the following sessions:

AMD1

AMD2

AMD3

New durg treatments and technologies 1 and 2

Browsed ‘Posters’ and within that the following sessions: AMD


63

1026

1027

1028

1029

1030

1031

1032

1033

1034

1035

1036

1037

1038

1039

1040

1041

1042

1043

1044

1045

1046

1047

1048

1049

1050

1051

A.19 SUPPLEMENTARY SEARCHES UNDERTAKEN FOR PEGAPTANIB TRIALS

Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R)

<1946 to Present>. Searched 17 March 2014

1 (pegaptanib or macugen$ or 222716-86-1 or 2H1PA8H1EN).ti,ab,rn. (514)

2 randomized controlled trial.pt. (367280)

3 controlled clinical trial.pt. (87861)

4 randomized.ab. (287121)

5 placebo.ab. (151535)

6 drug therapy.fs. (1675625)

7 randomly.ab. (208366)

8 trial.ab. (297423)

9 groups.ab. (1329823)

10 or/2-9 (3283177)

11 1 and 10 (391)

12 exp animals/ not humans/ (3901065)

13 11 not 12 (385)

14 remove duplicates from 13 (380)

CENTRAL on the Cochrane Library. Searched 17/03/14

#1 pegaptanib or macugen* or 222716-86-1 or 2H1PA8H1EN in Trials 91

64

1052

1053

1054

1055

1056

1057

1058

1059

1060

1061

1062

1063

1064

1065

1066

1067

1068

1069

1070

1071

1072

1073

1074

1075

1076

1077

APPENDIX 1B: Excluded Records with Reasons for Exclusion

65

1078

1079

1080

1081

1082

1083

1084

1085

1086

1087

1088

1089

1090

1091

Table B.1: Excluded records (94)

ReferenceReason for Exclusion

Abedi F, Wickremasinghe S, Islam AFM, Inglis KM, Guymer RH. Anti-

VEGF treatment in neovascular age-related macular degeneration: a

treat-and-extend protocol over 2 years. Retina. 2014;34(8):1531-8.

Ineligible

study design

Alcon Research. LHA510 Proof-of-Concept Study as a Maintenance

Therapy for Patients With Wet Age-Related Macular Degeneration. In:

ClinicalTrials.gov [internet]. Bethesda. US National Library of

Medicine. 2015. Available from

https://ClinicalTrials.gov/show/NCT02355028. Identifier:

NCT02355028

Trial register

record (no

results at time

of search)

Altaweel MM, Daniel E, Martin DF, Mittra RA, Grunwald JE, Lai MM,

et al. Outcomes of eyes with lesions composed of >50% blood in the

Comparison of Age-related Macular Degeneration Treatments Trials

(CATT). Ophthalmology. 2015;122(2):391-98.e5.

Ineligible

patient

population

Arnold J, Guymer R, Kurstjens N, Markey C. Phase IV ranibizumab

study investigating the extent of retinal fluid resolution in patients with

neovascular age-related macular degeneration (NAMD): The fluid

study [conference abstract]. Clin Experiment Ophthalmol. 2014;

42(Suppl S1): 109. Available from:

http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/638/CN-

01086638/frame.html

Abstract only

- insufficient

information

Australian National University. The RAAMP study. Ranibizumab

versus aflibercept for age-related macular degeneration, using

multifocal objective pupil perimetry. In: Australian New Zealand

Clinical Trials Registry (ANZCTR) [internet]. Sydney. National Health

and Medical Research Council (NHMRC) Clinical Trials Centre -

University of Sydney. 2014. Available from

http://www.anzctr.org.au/ACTRN12614000497606.aspx. Identifier:

Trial register

record (no

results at time

of search)

66

1092

1093

2


ACTRN12614000497606

Azienda Ospedaliera Universitaria Integrata. A randomized controlled

multicentre study to assess the non-inferiority of the safety of

bevacizumab compared to ranibizumab administered by intravitreal

injection in patients with macular degeneration or other exudative not

age-related macular. In: EU Clinical Trials Register [internet]. London.

European Medicines Agency. 2014. Available from

https://www.clinicaltrialsregister.eu/ctr-search/search?

query=eudract_number:2013-000133-12. Identifier: EUCTR2013-

000133-12-IT

Trial register

record (no

results at time

of search)

Bakri SJ, Moshfeghi DM, Francom S, Rundle AC, Reshef DS, Lee PP,

et al. Intraocular pressure in eyes receiving monthly ranibizumab in 2

pivotal age-related macular degeneration clinical trials.

Ophthalmology. 2014;121(5):1102-8.

Ineligible

outcomes

Barikian A, Mahfoud Z, Abdulaal M, Safar A, Bashshur ZF. Induction

with intravitreal bevacizumab every two weeks in the management of

neovascular age-related macular degeneration. Am J Ophthalmol.

2015;159(1):131-7.

Dosing study

Bayer HealthCare AG. A randomized, double-masked, sham-

controlled phase 3b/4 study of the efficacy, safety, and tolerability of

intravitreal aflibercept monotherapy compared to aflibercept with

adjunctive photodynamic therapy as indicated in subjects with

polypoidal choroidal vasculopathy (PLANET) - Aflibercept in

polypoidal choroidal vasculopathy. In: EU Clinical Trials Register

[internet]. London. European Medicines Agency. 2014. Available from


query=eudract_number:2013-004464-54. Identifier: 2013-004464-54

Trial register

record (no

results at time

of search)

Bayer, Regeneron Pharmaceuticals. Japanese Treat and Extend

Study of Aflibercept in Neovascular Age-related Macular

Trial register

record (no

673


Degeneration. In: ClinicalTrials.gov [internet]. Bethesda. US National

Library of Medicine. 2014. Available from


NCT02305238

results at time

of search)

Bayer. Special Drug Use Investigation of EYLEA for Myopic Choroidal

Neovascularization. In: ClinicalTrials.gov [internet]. Bethesda. US

National Library of Medicine. 2014. Available from


NCT02260687

Trial register

record (no

results at time

of search)

Bhisitkul RB, Mendes TS, Rofagha S, Enanoria W, Boyer DS, Sadda

SR, et al. Macular atrophy progression and 7-year vision outcomes in

subjects from the ANCHOR, MARINA, and HORIZON studies: the

SEVEN-UP study. Am J Ophthalmol. 2015;159(5):915-24.e2.

Ineligible

study design

Biocad. Safety and Efficacy Study of BCD-021 Compared to

Lucentis® in Patients With Neovascular Wet Age-related Macular




NCT02036723

Trial register

record (no

results at time

of search)

Bioeq GmbH. Efficacy and safety of the biosimilar ranibizumab

FYB201 in comparison to Lucentis in patients with neovascular age-

related macular degeneration (COLUMBUS-AMD). In: EU Clinical

Trials Register [internet]. London. European Medicines Agency. 2015.

Available from https://www.clinicaltrialsregister.eu/ctr-search/search?


001961-20-AT

Trial register

record (no

results at time

of search)

Braun BC, Schneider U, Henrich B, Hatz K, FuchsjÃ¤ger-Mayrl G,

Pruente C. Evaluation of Re-Treatment Indications in a Randomized,

Double-masked, Phase IIIb-Study Comparing LucentisÂ®

Abstract only

- insufficient

information

684


Monotherapy versus PDT Combined With LucentisÂ® in Patients With

Subfoveal Choroidal Neovascularisation [conference abstract]. Invest

Ophthalmol Vis Sci. 2008; 49(13): ARVO E- abstract 1172. Available

from:


00793673/frame.html

Bressler NM, Rosenfeld PJ, Lim JI, Group VIMS. A Phase II Placebo -

Controlled, Double - Masked, Randomized Trial – Verteporfin in

Minimally Classic CNV due to AMD (VIM). Invest Ophthalmol Vis Sci.

2003;44(13):1100.

Abstract only

- insufficient

information

Canadian Agency For Drugs And Technologies In Health (CADTH).

Aflibercept (Eylea - Bayer Inc.) indication: wet age-related macular

degeneration (Structured abstract). HTA Database. 2014; (1):

Available from:

http://onlinelibrary.wiley.com/o/cochrane/clhta/articles/HTA-

32015000167/frame.html

Review of

trials already

included

Canadian Agency for Drugs and Technologies in Health (CADTH).

CDR clinical review report for Aflibercept (Eylea). Ottawa: CADTH;

2015. Available from:

https://www.cadth.ca/sites/default/files/cdr/clinical/SR0361_Eylea_CL

_Report.pdf.

Review of

trials already

included

Canadian Agency for Drugs and Technologies in Health (CADTH).

CDR pharmacoeconomic review report for Aflibercept (Eylea).

Ottawa: Canadian Agency for Drugs and Technologies in Health;

2015. Available from:

https://www.cadth.ca/sites/default/files/cdr/pharmacoeconomic/SR036

1_Eylea_PE_Report.pdf.

Review of

trials already

included

Chakravarthy U, Adamis AP, Cunningham ET, Goldbaum M, Guyer

DR, Katz B, et al. Year 2 efficacy results of 2 randomized controlled

Ineligible

study design

695


clinical trials of pegaptanib for neovascular age-related macular

degeneration. Ophthalmology. 2006;113(9):1508-21.

Chakravarthy U, Jaffe GJ. Dual Antagonism of Platelet Derived

Growth Factor (Fovista 1.5 mg) and Vascular Endothelial Growth

Factor (Lucentis 0.5 mg) Results in Reduced Subretinal Fibrosis and

Neovascular Growth. In: Annual Meeting - American Academy of

Opthalmology, Chicago; Tuesday, October 21. 2014. PA092

Retrospective

analysis

Chang TS, Fine JT, Alexander S, Bressler N. Ranibizumab (Lucentis)

Self-Reported Vision Specific Quality of Life Through 12 Months in

Age-Related Macular Degeneration Patients with Minimally Classic or

Occult-with-No-Classic Choroidal Neovascularization in a Phase III

Randomized Clinical Trial [conference presentation]. In: The Macula

Society, San Diego; 2006. 106

Results of

MARINA and

ANCHOR

trials

Ciulla TA, Cuilla TA, Ying G-S, Maguire MG, Martin DF, Jaffe GJ, et

al. Influence of the Vitreomacular Interface on Treatment Outcomes in

the Comparison of Age-Related Macular Degeneration Treatments

Trials. Ophthalmology. 2015;122(6):1203-11.

Ineligible

comparator

Csaky KG, Dugel PU, Pierce AJ, Fries MA, Kelly DS, Danis RP, et al.

Clinical evaluation of pazopanib eye drops versus ranibizumab

intravitreal injections in subjects with neovascular age-related macular

degeneration. Ophthalmology. 2015;122(3):579-88.

Dosing study

for eye drops

Daniel E, Shaffer J, Ying G-S, Grunwald JE, Martin DF, Jaffe GJ, et

al. Outcomes in Eyes with Retinal Angiomatous Proliferation in the

Comparison of Age-Related Macular Degeneration Treatments Trials

(CATT). Ophthalmology. 2016;123(3):609-16.

Ineligible

comparator

Daniel E, Toth CA, Grunwald JE, Jaffe GJ, Martin DF, Fine SL, et al.

Risk of scar in the comparison of age-related macular degeneration

treatments trials. Ophthalmology. 2014;121(3):656-66.

Ineligible

outcomes

706


Department of Ophthalmology - Kagawa University Faculty of

Medicine. The switching therapy with Ranibizumab for Exudative Age-

related Macular Degeneration resistant to Aflibercept. In: UMIN

Clinical Trials Registry (UMIN-CTR) [internet]. Tokyo. University of

Tokyo Hospital. 2013. Available from https://upload.umin.ac.jp/cgi-

open-bin/ctr/ctr.cgi?

function=brows&action=brows&type=summary&langua

ge=E&recptno=R000014609. Identifier: JPRN-UMIN000012724

Trial register

record (no

results at time

of search)

Department of Ophthalmology - Kagawa University Faculty of

Medicine. Treatment outcomes in wet age-related macular

degeneration using a Treat-and-Extend regimen. In: UMIN Clinical

Trials Registry (UMIN-CTR) [internet]. Tokyo. University of Tokyo

Hospital. 2015. Available from

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?



Trial register

record (no

results at time

of search)

Desai S, Bhisitkul RB, Enoria W, Rofagha S, Boyer DS, Sadda SR, et

al. Visual outcomes and macular atrophy in non-study eyes in

ANCHOR/MARINA subjects (SEVEN-UP Study). Invest Ophthalmol

Vis Sci. 2015;56(7):2836.

Ineligible

study design

Dugel PU, Kunimoto D, Quinlan E, Jamal K, Goldenberg D, Mehta S,

et al. Anti-VEGF resistance in neovascular AMD: Role of PDGF

antagonism. Invest Ophthalmol Vis Sci. 2015;56(7):2826.

Non

comparative

subgroup

analysis

Duke University, Bausch & Lomb Incorporated. Adjunctive

Photodynamic Therapy + Aflibercept vs. Afilbercept Alone for PDA in

NV AMD. In: ClinicalTrials.gov [internet]. Bethesda. US National



Trial register

record (no

results at time

of search)

717


NCT02457026

El Gawhara Eye Center - Egypt. Prophylactic Ranibizumab in the

fellow eye in patients with wet type Age Related Macular

Degeneration. In: Australian New Zealand Clinical Trials Registry

[internet]. Sydney. National Health and Medical Research Council

(NHMRC) Clinical Trials Centre - University of Sydney. 2014.

Available from

http://www.anzctr.org.au/ACTRN12614000511639.aspx. Identifier:

ACTRN12614000511639

Trial register

record (no

results at time

of search)

Eldem BM, Muftuoglu G, Topbas S, Cakir M, Kadayifcilar S, Ozmert

E, et al. A randomized trial to compare the safety and efficacy of two

ranibizumab dosing regimens in a Turkish cohort of patients with

choroidal neovascularization secondary to AMD. Acta Ophthalmol.

2015;93(6):e458-64.

Dosing study

Fauser S, Viebahn U, Muether PS. Intraocular and systemic

inflammation-related cytokines during one year of ranibizumab

treatment for neovascular age-related macular degeneration. Acta

Ophthalmol. 2015;93(8):734-8.

Ineligible

study design

Folgar FA, Jaffe GJ, Ying G-S, Maguire MG, Toth CA, Comparison of

Age-Related Macular Degeneration Treatments Trials Research G.

Comparison of optical coherence tomography assessments in the

comparison of age-related macular degeneration treatments trials.

Ophthalmology. 2014;121(10):1956-65.

Ineligible

comparator

Frenkel REP, Fung AE, Shapiro H, Stoilov I. Low luminance vision

improves nearly twice as much as standard vision with ranibizumab

for neovascular age-related macular degeneration. Invest Ophthalmol

Vis Sci. 2015;56(7)

Ineligible

study design

Genentech Inc. Study of the Efficacy and Safety of the Ranibizumab

Port Delivery System for Sustained Delivery of Ranibizumab in

Trial register

record (no

728


Patients With Subfoveal Neovascular Age-Related Macular




NCT02510794

results at time

of search)

Gillies M, Hunyor A, Woodcock C, Walsh M, Kurstjens N. Design and

rationale of a clinical trial to measure the development of geographic

atrophy in patients undergoing anti-vascular endothelial growth factor

treatment for neovascular (WET) age-related macular degeneration:

The rival study [conference abstract]. Clin Experiment Ophthalmol.

2014; (Suppl S1): 113. Available from:


01103868/frame.html

Abstract only

- insufficient

information

Grunwald JE, Daniel E, Huang J, Ying G-S, Maguire MG, Toth CA, et

al. Risk of geographic atrophy in the comparison of age-related

macular degeneration treatments trials. Ophthalmology.

2014;121(1):150-61.

Ineligible

outcomes

Grunwald JE, Pistilli M, Ying G-S, Maguire MG, Daniel E, Martin DF,

et al. Growth of geographic atrophy in the comparison of age-related

macular degeneration treatments trials. Ophthalmology.

2015;122(4):809-16.

Ineligible

indication

Hospices Civils de Lyon. Phase II study evaluating the efficacy of

aflibercept for the treatment of choroidal neovascularization

complicating angioid streaks in young subjects: the ASTRID study. In:

EU Clinical Trials Register [internet]. London. European Medicines

Agency. 2015. Available from https://www.clinicaltrialsregister.eu/ctr-

search/search?query=eudract_number:2014-003661-18. Identifier:

EUCTR2014-003661-18-FR

Trial register

record (no

results at time

of search)

Hospices Civils de Lyon. Phase II study evaluating the efficacy of Trial register

739


aflibercept for the treatment of inflammatory choroidal

neovascularization in young subjects: the ALINEA study. In: EU

Clinical Trials Register [internet]. London. European Medicines



EUCTR2014-003695-23-FR

record (no

results at time

of search)

Hospital Authority - Hong Kong. A randomised control trial of anti-

VEGF in the Hospital Authority Setting – the AVIHA Trial: a

Neovascular AMD study. In: Chinese Clinical Trial Register [internet].

Chengdu. Chinese University of Hong Kong. 2014. Available from

http://www.chictr.org.cn/showprojen.aspx?proj=4819. Identifier:

ChiCTR-TRC-14004754

Trial register

record (no

results at time

of search)

Ikuno Y, Ohno-Matsui K, Wong TY, Korobelnik J-F, Vitti R, Li T, et al.

Intravitreal Aflibercept Injection in Patients with Myopic Choroidal

Neovascularization: The MYRROR Study. Ophthalmology.

2015;122(6):1220-7.

Ineligible

indication

Intas Biopharmaceuticals. To compare the safety and efficacy of

Ranibizumab of Intas Biopharmaceuticals Ltd. in comparison with

Lucentis in patients of wet Age related Macular Degeneration. In:

Clinical Trials Registry - India [internet]. New Delhi. National Institute

of Medical Statistics. 2013. Available from

http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7625.

Identifier: CTRI/2013/10/004063

Trial register

record (no

results at time

of search)

Kaiser PK, Grp TAPS. Verteporfin therapy of subfoveal choroidal

neovascularization in age-related macular degeneration: 5-year

results of two randomized clinical trials with an open-label extension -

TAP Report No. 8. Graefes Arch Clin Exp Ophthalmol

2006;244(9):1132-42.

Ineligible

study design

Kertes PJ, Sheidow TG, Williams RG, Greve M, Galic IJ, Rampakakis Abstract-

7410


E, et al. Canadian Treat-and-Extend Analysis Trial With Ranibizumab

in Patients With Neovascular AMD: Interim Analysis of the

CANTREAT Study. In: Annual Meeting - American Academy of

Ophthalmology, Las Vegas; Monday, November 16. 2015. PO486

insufficient

info. Listed in

CT.gov as

observational

NCT0210373

8. No results

Khanani A, Hill L, Tuomi L. Improvement in visual acuity following

ranibizumab treatment in neovascular age-related macular

degeneration patients with large pigment epithelial detachments: a

subgroup analysis of the HARBOR study [meeting abstract]. Invest

Ophthalmol Vis Sci. 2015;56(7):A5363.

Dosing study

Li J, Sun JH. Ranibizumab with transpupillary thermotherapy for

clinical efficacy in wet age-related macular degeneration. Int Eye Sci.

2014; 14(10): 1744-8. Available from:


01050614/frame.html

Ineligible

comparator

Li XX, Chen YX, Zhang JJ, Xu X, Cheung GM, Wu HL, et al.

Intravitreal aflibercept shows consistent outcomes in Asian and white

patients with wet age-related macular degeneration: novel results

from the SIGHT and VIEW studies. Invest Ophthalmol Vis Sci.

2015;56(7)

Combined

results of

SIGHT and

VIEW

Lloyd Clark W. Long-term Follow-up of Intravitreal Aflibercept Injection

for Neovascular AMD. In: Annual Meeting - American Academy of

Ophthalmology, Chicago; 20 October. 2014. PO534

Open label

extension of

VIEW I

Lotery AJ, Gibson J, Cree AJ, Downes SM, Harding SP, Rogers CA,

et al. Pharmacogenetic associations with vascular endothelial growth

factor inhibition in participants with neovascular age-related macular

degeneration in the IVAN Study. Ophthalmology. 2013;120(12):2637-

43.

Ineligible

outcomes

7511


Mahmood S, Roberts SA, Aslam TM, Parkes J, Barugh K, Bishop PN,

et al. Routine versus As-Needed Bevacizumab with 12-Weekly

Assessment Intervals for Neovascular Age-Related Macular

Degeneration: 92-Week Results of the GMAN Trial. Ophthalmology.

2015;122(7):1348-55.

Dosing study

Medizinische Universität Wien. Activity patterns of the cortical optic

area in wet age-related macular degeneration patients [fMRI analysis

of the visual cortex in neovascular age-related macular degeneration].

In: EU Clinical Trials Register [internet]. London. European Medicines



EUCTR2012-004758-27-AT

Trial register

record (no

results at time

of search)

Meredith TA, McCannel CA, Barr C, Doft BH, Peskin E, Maguire MG,

et al. Postinjection endophthalmitis in the comparison of age-related

macular degeneration treatments trials (CATT). Ophthalmology.

2015;122(4):817-21.

Insufficient

information

Mie University Graduate School of Medicine. Randomized controlled

phase IV trial of combination aflibercept and Kallidinogenase for

neovascular age-related macular degeneration. In: UMIN Clinical

Trials Registry (UMIN-CTR) [internet]. Tokyo. University of Tokyo

Hospital. 2013. Available from

https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?



Trial register

record (no

results at time

of search)

Moorfields Eye Hospital. The LEAVO study. In: ISRCTN Registry

[internet]. London. BioMed Central. 2014. Available from

http://isrctn.com/ISRCTN13623634. Identifier: ISRCTN13623634

Trial register

record (no

results at time

of search)

Nagoya City University Graduate School of Medical Sciences. Study Trial register

7612


of efficacy of aflibercept in neovascular age-related macular

degeneration (wAMD) with non-responder of ranibizumab. In: UMIN






record (no

results at time

of search)

Nagoya City University Graduate School of Medical Sciences. Study

of efficacy of aflibercept in neovascular age-related macular

degeneration (wAMD) with refractory of ranibizumab. In: UMIN






Trial register

record (no

results at time

of search)

Novartis Pharma. Comparison of systemic VEGF protein dynamics

following monthly intravitreal injections of 0.5 mg ranibizumab versus

2 mg aflibercept in patients with neovascular (wet) age-related

macular degeneration. In: EU Clinical Trials Register [internet].

London. European Medicines Agency. 2014. Available from



001182-27-DE

Trial register

record (no

results at time

of search)

Novartis Pharma. Efficacy of ranibizumab compared to aflibercept

bimonthly intravitreal injections on retinal thickness stabilityin in

patients with nAMD. In: EU Clinical Trials Register [internet]. London.

European Medicines Agency. 2013. Available from



Trial register

record (no

results at time

of search)

7713


002431-15-DE

Novartis Pharmaceuticals. A Comparison of Ranibizumab and

Aflibercept for the Development of Geographic Atrophy in (Wet) AMD

Patients. In: ClinicalTrials.gov [internet]. Bethesda. US National



NCT02130024

Trial register

record (no

results at time

of search)

Novartis Pharmaceuticals. Assess the Efficacy/Safety of Intravitreal

Ranibizumab in People With Vision Loss Due to Choroidal

Neovascularization. In: ClinicalTrials.gov [internet]. Bethesda. US



NCT01840410

Trial register

record (no

results at time

of search)

Novartis Pharmaceuticals. Efficacy of Ranibizumab Prn Treatment

Compared to Aflibercept Bimonthly Intravitreal Injections on Retinal

Thickness Stability in Patients With NAMD. In: ClinicalTrials.gov

[internet]. Bethesda. US National Library of Medicine. 2013. Available

from https://ClinicalTrials.gov/show/NCT01958918. Identifier:

NCT01958918

Trial register

record (no

results at time

of search)

Novartis Pharmaceuticals. Prospective study of safety and efficacy of

combination therapy using intravitreal triamcinolone acetonide and

ranibizumab versus ranibizumab monotherapy for neovascular age-

related macular degeneration. In: Chinese Clinical Trial Register

[internet]. Chengdu. Chinese University of Hong Kong. 2015.

Available from http://www.chictr.org.cn/showproj.aspx?proj=11249.

Identifier: ChiCTR-ICR-15006619

Trial register

record (no

results at time

of search)

Novartis Pharmaceuticals. Randomized Study for Efficacy and Safety

of Ranibizumab 0.5mg in Treat-extend and Monthly Regimens in

Patients With nAMD. In: ClinicalTrials.gov [internet]. Bethesda. US

Trial register

record (no

results at time

7814




NCT01948830

of search)

Novartis Pharmaceuticals. Systemic VEGF Protein Dynamics

Following Intravitreal Injections of Ranibizumab Versus Aflibercept in

Patients With Neovascular Age-related Macular Degeneration. In:




NCT02257632

Trial register

record (no

results at time

of search)

Novartis Pharmaceuticals. UNcovering the Difference Between

Ranibizumab and Aflibercept, Focusing on Systemic Anti-VEGF

Effects in Patients With neovascuLar AMD. In: ClinicalTrials.gov



NCT01988662

Trial register

record (no

results at time

of search)

Ohr Pharmaceutical Inc. Effect of Squalamine Lactate Ophthalmic

Solution, 0.2% in Subjects With Neovascular Age-Related Macular




NCT02511613

Trial register

record (no

results at time

of search)

Patel PJ, Rubin GS, Chen FK, da Cruz L, Tufail A, Investigators

ABCT. Impact of Anti-vascular Endothelial Growth Factor Therapy on

Reading Performance in Age-related Macular Degeneration: A

Randomized Controlled Trial. Invest Ophthalmol Vis Sci.

2015;56(7):4794.

Abstract only

- insufficient

information

Piri N, Ahmadieh H, Taei R, Soheilian M, Karkhaneh R, Lashay A, et

al. Photodynamic Therapy and Intravitreal Bevacizumab with Versus

Ineligible

intervention

7915


without Triamcinolone for Neovascular Age-related Macular

Degeneration; a Randomized Clinical Trial. J Ophthalmic Vis Res.

2014;9(4):469-77.

Pistilli M, Ying G-S, Toth CA, Jaffe GJ, Martin DF, Grp CR. Resolution

of Retinal Fluid on Optical Coherence Tomography in the Comparison

of AMD Treatments Trials (CATT). Invest Ophthalmol Vis Sci.

2015;56(7):1657.

Abstract only

- insufficient

information

Pusan National University Hospital. Effect of Intravitreal VEGF-Trap

Eye on Polypoidal Choroidal Vasculopathy. In: ClinicalTrials.gov



NCT01950741

Trial register

record (no

results at time

of search)

Ramsay CR. Aflibercept solution for injection for the treatment of wet

age-related macular degeneration (ID519) [project record: report

unpublished as yet]. Southampton: NIHR; 2013. Available from:

http://onlinelibrary.wiley.com/o/cochrane/clhta/articles/HTA-

32013000885/frame.html.

Review of

trials already

included

Ranibizumab (Lucentis) in high myopia with neovascularization. Better

short-term visual acuity but serious adverse effects. Prescrire Int.

2015;24(161):151.

Abstract only

- insufficient

information

Rezar S, Sacu S, Eibenberger K, Buehl W, Krall C, Weigert G, et al.

Role of additional dexamethasone treatment for the management of

persistent choroidal neovascularization secondary to age-related

macular degeneration. In: ARVO 2015 Annual Meeting, Denver; 4

May. 2015. 1280, A203

Abstract only

- insufficient

information

Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K, Group S-

US. Seven-year outcomes in ranibizumab-treated patients in

ANCHOR, MARINA, and HORIZON: a multicenter cohort study

Ineligible

study design

8016


(SEVEN-UP). Ophthalmology. 2013;120(11):2292-9.

Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K, Grp S-US.

Seven-Year Outcomes in Ranibizumab-Treated Patients in ANCHOR,

MARINA, and HORIZON. Ophthalmology. 2013;120(11):2292-99.

Ineligible

study design

Russo A, Costagliola C, Delcassi L, Romano MR, Semeraro F. A

randomised controlled trial of ranibizumab with and without ketorolac

eyedrops for exudative age-related macular degeneration. Br J

Ophthalmol. 2013;97(10):1273-6.

Ineligible

intervention

Saturnino LTM, Silveira MR, Guerra AA, Acurcio FDA. Efficacy and

Safety of Ranibizumab and Bevacizumab in Treatment for Age

Related Macular Degeneration. Value Health. 2013;16(7):A667-A68.

Abstract only

- insufficient

information

Saviano S, Piermarocchi R, Leon PE, Mangogna A, Zanei A,

Cavarzeran Sc F, et al. Combined therapy with bevacizumab and

photodynamic therapy for myopic choroidal neovascularization: A

one-year follow-up controlled study. insert correct info here.

2014;7(2):335-9.

Ineligible

study design

Schmidt-Erfurth U, Waldstein SM, Deak G-G, Kundi M, Simader C.

Pigment epithelial detachment followed by retinal cystoid

degeneration leads to vision loss in treatment of neovascular age-

related macular degeneration. Ophthalmology. 2015;122(4):822-32.

Ineligible

outcomes

Selim A, Kocak N, Aslankara H, Kaynak S. Comparative study of

photodynamic therapy monotherapy versus triple management in age-

related macular degeneration. Turk J Med Sci. 2014;44(5):889-95.

Ineligible

intervention

Shi X, Wei W, Zhang C. Intravitreal ranibizumab therapy versus

photodynamic therapy for idiopathic choroidal neovascularization: a

comparative study on visual acuity, retinal and choroidal thickness.

Chin Med J. 2014;127(12):2279-85.

Ineligible

study design

Simader C, Ritter M, Bolz M, Deak GG, Mayr-Sponer U, Golbaz I, et Dosing study

8117


al. Morphologic parameters relevant for visual outcome during anti-

angiogenic therapy of neovascular age-related macular degeneration.

Ophthalmology. 2014;121(6):1237-45.

Sin M, Chrapek O, Karhanova M, Pracharova Z, Langova K, Rehak J.

Progression of macular atrophy after PDT combined with the COX-2

inhibitor Nabumetone in the treatment of neovascular ARMD. Biomed

Pap Med Fac Univ Palacky Olomouc Czech Repub. 2014;158(1):138-

43.

Ineligible

intervention

Singer MA. Safety of Intravitreal Aflibercept Injection From RE-VIEW

in Neovascular AMD. In: Annual Meeting - American Academy of

Ophthalmology, Las Vegas; 15 November. 2015. PO212

Abstract only

- extension of

VIEW trials

Sizmaz S, Kucukerdonmez C, Kal A, Pinarci EY, Canan H, Yilmaz G.

Retinal and choroidal thickness changes after single anti-VEGF

injection in neovascular age-related macular degeneration:

ranibizumab vs bevacizumab. Eur J Ophthalmol. 2014;24(6):904-10.

Ineligible

outcomes

St. Michael's Hospital Toronto. Intravitreal Aflibercept in Wet Age

Related Macular Degeneration Patients With an Incomplete Response

to Routine Ranibizumab Injections. In: ClinicalTrials.gov [internet].

Bethesda. US National Library of Medicine. 2014. Available from


NCT02002377

Trial register

record (no

results at time

of search)

Sulzbacher F, Sacu S, Roberts PK, Munk MR, Kroh ME, Kaider A, et

al. Relationship of Retinal morphology and Sensitivity in Neovascular

Age-related Macular Degeneration (NAMD). Comparision of

Ranibizumab versus Aflibercept treatment over 1 year. Invest

Ophthalmol Vis Sci. 2015;56(7):A1521.

Ineligible

study design

Tyrogenex. X-82 to Treat Age-related Macular Degeneration. In:



Trial register

record (no

results at time

8218



NCT02348359of search)

University Health Network Toronto. Intraocular Cytokines in Non-

responders to Ranibizumab Treatment for Neovascular AMD. In:




NCT02218177

Trial register

record (no

results at time

of search)

Willoughby AS, Ying G-S, Toth CA, Maguire MG, Burns RE, Grunwald

JE, et al. Subretinal Hyperreflective Material in the Comparison of

Age-Related Macular Degeneration Treatments Trials.

Ophthalmology. 2015;122(9):1846-53.e5.

Ineligible

comparator

Zehetner C, Kralinger MT, Modi YS, Waltl I, Ulmer H, Kirchmair R, et

al. Systemic levels of vascular endothelial growth factor before and

after intravitreal injection of aflibercept or ranibizumab in patients with

age-related macular degeneration: a randomised, prospective trial.

Acta Ophthalmol. 2015;93(2):e154-9.

Ineligible

outcomes

83

1094

1095

19

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