https://links.lww.com/ICO/A878

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Appendices Appendix A: EMBASE search strategy

1. Boston keratoprosthesis.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating

subheading word]

2. Boston KPro.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

3. Boston type 1 keratoprosthesis.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

4. KProtype 1.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

5. Boston type 1 KPro.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

6. type 1 keratoprosthesis.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating

subheading word]

7. Dohlman Doane.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

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8. Dohlman Doane keratoprosthesis.mp. [mp=title, abstract, heading word, drug trade name, original title, device manufacturer, drug manufacturer, device trade name, keyword, floating subheading word]

9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8

10. limit 9 to (human and English language and adult <18 to 64 years>) 11. limit 9 to (human and English language and aged <65+ years>) 12. 10 or 11

Appendix B: OVID Medline search strategy

1. Boston keratoprosthesis.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

2. Boston KPro.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

3. Boston type 1 keratoprosthesis.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

4. KProtype 1.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44

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5. Boston type 1 KPro.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

6. type 1 keratoprosthesis.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

7. Dohlman Doane.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

8. Dohlman Doane keratoprosthesis.mp. [mp=title, abstract, original title, name of substance word, subject heading word, keyword heading word, protocol supplementary concept word, rare disease supplementary concept word, unique identifier, synonyms]

9. 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8

10. limit 9 to (English language and humans and "all adult (19 plus years)")

Appendix C: CENTRAL search strategy

#1 Boston keratoprosthesis

#2 Boston KPro

#3 Boston type 1 keratoprosthesis

#4 KProtype 1

#5 Boston type 1 KPro

#6 type 1 keratoprosthesis

#7 Dohlman Doane keratoprosthesis 45

46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68

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#8 Dohlman Doane

#9 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 69

70 71 72 73 74 75 76 77 78 79 80 81 82 83

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Appendix D: Study characteristics table

References Study Design Location Of Data Collected

Total Number Of Eyes Mean Age (range)

Mean Follow-up Time In Months

(range)

Indications/Preoperative diagnoses Number Of Eyes Followed

up To 2 years

Number Of Eyes Followed

Up To 5 years Ahmad, 2015¹⁵ Retrospective

observational

John Hopkins Wilmer Eye Institute, Baltimore USA

59 65 (21-96) 37.8 Failed corneal transplantation (78%), extensive corneal neovascularisation, severe retinal disease and hypotony, chronic

uveitis (all 5.1%), SJS, MMP, severe atopic keratoconjunctivitis, aniridia (all 1.7%).

Unspecified Unspecified

Ahmad, 2016¹⁶ Retrospective observational

5 USA tertiary centres (Albany Medical Centre, Flaum Eye Institute, Stein

Eye Institute, Wills Eye Institute, Wilmer Eye

Institute)

148 63.2 48.9 (7-104) Glaucoma (55%), Fuchs dystrophy/bullous

keratopathy/keratoconus (39.2%), Unknown aetiology, OSD (both 17.5%), Congenital corneal abnormalities (14.2%), Infection

(11.2%).

Alexander, 2015³⁹ Retrospective observational

Steine Eye Institute, California, USA

209 58.7 (3-95) 27.8 (0.5-106.5) Previously failed graft (46.6%), SJS (11.6%), LCSD (10.3%), chemical injury (7.7%), repeat KPro (12%), corneal vascularisation (4.7%),

MMP, aniridia, other (1.7%), thermal burn (1.3%), atopic keratoconjunctivitis (0.9%).

108 25

Aravena, 2016¹⁴ Retrospective observational

Steine Eye Institute, California USA

149 61 (17-88) 66 (10-95) Failed corneal transplant (70.5%), failed KPro (1.3%), SJS (6.7%), chemical injury (7.4%), corneal scarring/vascularisation (7.4%),

aniridia (2.7%), medication toxicity (2%), MMP (2%).

108 55

Brown, 2014¹⁷ Retrospective observational

University of Iowa Hospitals and Clinics

9 64 (50-84) 49.3 HSV infection (55.5%), HZV infection (44.4%). 9 Unspecified

Chang, 2015¹⁸ Retrospective observational

Massachusetts Eye and Ear Infirmary

43 58 (27-94) 39 (12-60) Aniridic keratopathy (25.6%), LSCD, Salzmann modular degeneration (7%), herpetic keratopathy (14%), keratitis (11.6%), non-herpetic neurotrophic keratopathy, trauma, albinism, corneal ulcer (4.7%), Fuchs endothelial dystrophy, bullous keratopathy, endophthalmitis, keratoconus, trachoma, unknown, sclerocornea

(2.3%).

35 Unspecified

84

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(range)

up To 2 years

Up To 5 years De la Paz, 2014¹⁹ Retrospective

observational

Centro de Oftalmología Barraquer, Barcelona and

the University Eye Clinic, Salzburg

67 54 (13-87) 26 (1-54) Chemical/thermal burn (19.7%), autoimmune disease (26.2%), bullous keratopathy (9.8%), aniridia (8.1%), leukoma (11.5%), trauma (6.6%), corneal opacity, corneal ectatic disease (4.9%),

neurotrophic keratopathy (3.3%), calcific keratopathy, LSCD, trachoma, congenital glaucoma (1.6%).

Unspecified 0

De Oliveira, 2014²⁰

Prospective observational

Federal University of São Paulo

30 - 32 (1-55) Failed grafts (53.3%), chemical injury (33.3%), SJS (13.3%). Unspecified 0

Gibbons 2018³⁶ Retrospective observational

Bascom Palmer Eye Institute, Miami USA

45 66.7 (49.9-

83.5)

51 (12-102) Previously failed graft (89%), chronic ocular hypotony (9%), trauma (2%)

Goins, 2016³⁸ Retrospective observational

75 57.7 (0.6-

91.4)

41.4 (0.8-82.8) Previously failed graft (80%), aniridia (9.3%), paediatric glaucoma (4%), cicatricial conjunctival disorders (2.7%), chemical injury, HZV

keratitis, traumatic 5th nerve palsy (all 1.3%)

61 31

Goldman, 2013⁴² Retrospective observational

Steine Eye Institute, California, USA

83 62.8 (15-

95)

28.2 (6-84) Failed previous PK (63.6%), failed previous KPro(11.8%), chemical injury (7.3%), limbal stem cell deficiency (5.5%), Stevens–Johnson syndrome (5.5%), aniridia (3.6%), atopic keratoconjunctivitis

(21.8%), and corneal scarring/vascularization (0.9%).

45 7

Gu, 2016²¹ Retrospective observational

Zhongshan Ophthalmic Center, Southern China

19 42.7 (29-

62)

41.3 (36-56) Severe chemical burns (100%) 19 0

Hager, 2016²² Retrospective observational

24 65.3 (41-

87)

28.9 (7–63) Previous failed keratoplasty (100%) Unspecified Unspecified

Harissi-Dagher, 2008²³

Retrospective observational

Massachusetts Eye and Ear Infirmary

30 54 (19-85) 35 (1-108) Mechanical trauma (20%), chemical trauma (70%), thermal burns Unspecified Unspecified

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(range)

up To 2 years

Up To 5 years (10%)

Hassanaly, 2014²⁴ Retrospective observational

University of Montreal Hospital Center

26 56 (28-72) 28.7 (4-50) Aniridia (100%) 19 0

Jasinskas, 2013²⁵ Retrospective observational

Lithuanian University of Health Sciences

5 50 (25-80) 26.4 (12-36) Failed corneal transplant (60%), corneal leukoma after thermal and mechanical injuries (20%), corneal leukoma after chemical

injury (20%

3 0

Kang, 2018⁴⁰ Retrospective observational

University of Illinois Eye and Ear infirmary

56 51.1 60 Chemical/thermal injuries (29%), aniridia (25%), autoimmune

disease (18%), infectious keratitis/neurotrophic cornea (4%), gelatinous corneal dystrophy, ectrodactyly ectodermal

dysplasia/LSCD (7%), uveitis/hypotony (11%)

52 29

Kosker, 2015²⁶ Retrospective observational

Wills Eye Hospital, Philadelphia

37 60.3 (6-88) 31.7 (12-78) Previous failed graft (75.7%), bullous keratopathy (5.4%), chemical burn, other (8.1%), keratoconus (2.7%).

21 8

Lekhanont, 2014³⁷

Ramathibodi Hospital, Bangkok, Thailand

42 49.3 (7-78) 64.9 (48-88) Previously failed graft (59.5%), SJS (11.9%), chemical injury (9.5%), bullous keratopathy (4.8%), corneal dystrophy (4.8%), LCSD

unknown cause, LCSD neurofibromatosis (both 4.8%)

42 34

Magalhaes, 2013²⁷

Federal University of São Paulo

10 41.5 (27-

58)

25.7 (13-41) Ocular burns (100%) 6 0

Muzychuk, 2017⁴³

Prospective randomised controlled

trial

37 63 (28-94) 39 (24-60) Other (86.5%), chemical burns (8.1%), autoimmune (5.4%) 36 26

Palioura, 2013²⁸ Retrospective Massachusetts Eye and Ear 8 71.3 (55- 38 MMP (100%) 8 Unspecified

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(range)

up To 2 years

Up To 5 years

observational Infirmary 94)

Patel, 2016²⁹ Retrospective observational

Wills Eye Hospital, Philadelphia or affiliated

institutions

43 64.6 40.4 Not specified. 24 10

Phillips, 2014³⁰ Retrospective observational

9 55.4 (33-

75)

40.7 (29-60) Chemical burn (88.8%), thermal burn (11.1%). 9 1

Phillips, 2015³¹ Retrospective observational

4 68.3 (60-

80)

47 (27-69) Failed corneal transplant and iridocorneal endothelial syndrome (100%)

4 1

Salvador-Culla, 2016³²

Hospital Elías Santana, Santo Domingo, Dominican

Republic

42 35.4 (22-

57)

40.2 (6-98) Chemical burns (100%) 35 13

Samarawickrama , 2018⁴¹

Moorfields Eye Hospital, London, UK

39 56.9 (24.8–

88.4)

28.4 (12–56) Bullous keratopathy (56%), limbal stem cell failure (15%), ectasia (10%), congenital anterior segment dysgenesis (10%), aniridia

(8%), primary graft (5%)

Unspecified 0

Srikumaran, 2014³³

5 unspecified USA tertiary centres

139 63.9 46.7 (1-104) OSD (23%), congenital corneal abnormalities (12.9%), Known/presumed infectious keratitis (12.2%), Bullous keratopathy/dystrophy (35.3%), unknown (16.5%)

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(range)

up To 2 years

Up To 5 years Vaillancourt,

2017³⁴

22 57.7 (35-

86)

24 Aniridia (55%), post-traumatic corneal scar, HSV corneal scar, neurotrophic keratopathy, bullous keratopathy, lattice dystrophy

(9%).

21 0

Wang, 2014³⁵ Retrospective observational

110 60.8 (21-

98)

40 (1-68) Aniridia (24.5%), bullous keratopathy (17.3%), herpetic keratitis (12.7%), trauma, miscellaneous (11.8%), chemical burn (8.2%),

autoimmune, Fuchs dystrophy, infectious ulcers (2.7%)

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Appendix E – Non-randomised study quality assessment using MINORS tool Study Clearly stated aim Inclusion of consecutive

patients Prospective collection

of data Appropriate Endpointsfor aim of study Unbiased assessment ofthe study endpoint Follow-up periodappropriate for aim Loss to follow-up <5% Prospective calculation

of study size Adequate control group Contemporary groups Baseline equivalence of groups Adequate statistical analysis Total

Ahmad 2015 2 2 0 2 0 2 2 2 N/A N/A N/A N/A 12

Ahmad 2016 2 2 0 1 0 2 2 2 N/A N/A N/A N/A 11

Alexander 2015 1 2 0 1 0 1 1 0 1 2 1 2 12

Aravena 2016 1 2 0 1 0 1 1 0 N/A N/A N/A N/A 6

Chang 2015 1 1 0 2 0 2 1 0 N/A N/A N/A N/A 7

Brown 2014 2 2 0 2 0 2 2 1 0 2 1 1 15

De la Paz 2014 1 0 0 2 0 2 1 2 N/A N/A N/A N/A 8

De Oliveira 2014 2 1 2 2 0 2 1 2 N/A N/A N/A N/A 12

Gibbons 2018 2 2 0 1 0 1 1 0 N/A N/A N/A N/A 7

Goins 2016 2 2 0 2 0 1 1 1 N/A N/A N/A N/A 9

Goldman 2013 2 2 0 2 0 1 1 0 N/A N/A N/A N/A 8

Gu 2016 1 2 0 2 0 2 2 2 0 2 2 1 16

Hager 2016 1 1 0 2 0 2 1 1 N/A N/A N/A N/A 8

Harissi-Dagher 2008

1 2 0 2 0 2 1 0 N/A N/A N/A N/A 8

Hassanaly 2014 1 1 0 2 0 1 1 2 N/A N/A N/A N/A 8

Jasinskas 2013 0 1 0 1 0 2 1 0 N/A N/A N/A N/A 5

Kang 2018 1 2 0 1 0 2 2 2 1 2 2 1 16

Kosker 2015 1 2 0 2 0 2 1 1 N/A N/A N/A N/A 9

Lekhanont 2014 1 2 2 0 0 2 1 2 N/A N/A N/A N/A 10

Magalhaes 2013 2 1 2 2 0 2 1 2 N/A N/A N/A N/A 12

85

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Palioura 2013 1 2 0 1 0 2 2 2 0 0 0 2 12

Patel 2016 2 2 0 1 0 1 1 2 0 2 1 2 14

Phillips 2014 1 2 0 2 0 2 2 2 N/A N/A N/A N/A 11

Phillips 2015 1 2 0 2 0 2 1 0 N/A N/A N/A N/A 8

Salvador-Culla 2016

2 2 0 2 0 2 1 2 N/A N/A N/A N/A 11

Samarawickram a 2018

1 2 0 1 0 1 1 0 N/A N/A N/A N/A 6

Srikumaran 2014

1 2 0 2 0 2 2 2 N/A N/A N/A N/A 11

Vaillancourt 2017

2 2 0 2 0 1 1 2 0 1 2 2 16

Wang 2015 2 2 0 2 0 1 1 2 N/A N/A N/A N/A 10

86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104

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Appendix F: Randomised study quality assessment using JBI critical appraisal checklist for randomised control trials

Yes No Unclear N/A

1. 1. Was true randomization used for assignment of participants to treatment groups?

X □ □ □

2. Was allocation to treatment groups concealed? □ X □ □

3. Were treatment groups similar at the baseline? X □ □ □

4. Were participants blind to treatment assignment? □ X □ □ 5. Were those delivering treatment blind to treatment

assignment?

□ X □ □

6. Were outcomes assessors blind to treatment assignment? □ □ X □ 7. Were treatment groups treated identically other than the

intervention of interest?

X □ □ □

8. Was follow up complete and if not, were differences between groups in terms of their follow up adequately described and analysed?

X □ □ □

9. Were participants analysed in the groups to which they were randomized?

X □ □ □

10. Were outcomes measured in the same way for treatment groups?

X □ □ □

11. Were outcomes measured in a reliable way? X □ □ □

12. Was appropriate statistical analysis used? X □ □ □

13. Was the trial design appropriate, and any deviations from the standard RCT design (individual randomization, parallel groups) accounted for in the conduct and analysis of the trial?

X □ □ □

105 106 107 108 109

110 111