1. LASIK is safe in the long run; looking back at 50 years of lamellar corneal surgery Dan Z Reinstein MD MA(Cantab) FRCSC FRCOphth 1,2,3,4 Timothy J Archer, MA(Oxon), DipCompSci(Cantab) 1 1. London Vision Clinic, London, UK 2. St. Thomas’ Hospital - Kings College, London, UK 3. Weill Medical College of Cornell University, New York, USA 4. Centre Hospitalier National d’Ophtalmologie, (Pr. Laroche) , Paris, France

2. What do we know about the long-term safety of LASIK?

3. National Institute for Clinical Excellence – UK “ guidance on the use of new and existing medicines, treatments and procedures within the NHS”

6. Published Long-Term PRK Outcomes - Myopia Stability Safety 136 eyes Mean SE: -11.40 D Summit Technology UV 200 Optical zone: 4 mm No ectasia

7. Published Long-Term LASIK Outcomes - Myopia Stability Safety 33 eyes Mean SE: -11.40 D Schwind Keratom I Chiron ALK 130 Optical zone: 5.5 or 6 No ectasia

8. Published Long-Term LASIK Outcomes - Hyperopia 125 eyes Mean SE: +3.84 D Chiron Technolas Keracor 117C Chiron Corneal Shaper 160 Optical zone: 5.5 mm Stability Safety 5% lost 2 lines No ectasia

9. Media Response to the NICE Report

10. NICE Request a Systematic Review

11. What else do we know about the long-term safety of LASIK? History of LASIK: Keratomileusis

17. Jose Barraquer: Keratomileusis

22. Keratomileusis Early Cohort vs Modern LASIK Keratomileusis LASIK Range of myopia Up to -27.00 D 86% above -7.01 D Rarely treated above -10.00 D Screening for keratoconus None, keratoconus unknown Topography unavailable Awareness of keratoconus Astigmatism, steep & thin corneas Front & back surface topography Future advances – epithelial thickness profiles, corneal stiffness Depth of keratectomy Deep resection: 300-350 µm in all eyes Original microkeratome: inaccurate & imprecise Microkeratomes more accurate & precise Thin flaps commonly used: avg 110 µm Accurate measurement of corneal thickness and residual stromal bed Low myopia - low ablation depths Ectasia 2.8% from the original cohort ~ 0.06% (more later)

23. Keratomileusis Early Cohort vs Modern LASIK Keratomileusis LASIK Range of myopia Up to -27.00 D 86% above -7.01 D Rarely treated above -10.00 D Screening for keratoconus None, keratoconus unknown Topography unavailable Awareness of keratoconus Astigmatism, steep & thin corneas Front & back surface topography Future advances – epithelial thickness profiles, corneal stiffness Depth of keratectomy Deep resection: 300-350 µm in all eyes Original microkeratome: inaccurate & imprecise Microkeratomes more accurate & precise Thin flaps commonly used: avg 110 µm Accurate measurement of corneal thickness and residual stromal bed Low myopia - low ablation depths Ectasia 2.8% from the original cohort ~ 0.06% (more later)

24. What else do we know about the long-term safety of LASIK? Screening for Keratoconus

25. Topography Screening for Keratoconus

26. Pentacam Screening for Keratoconus

29. LASIK / PRK in Keratoconus / Forme Fruste KC? ? Diagnosis LASIK PRK Normal Keratoconus Forme Fruste Keratoconus

33. “ Artemis 1” (ArcScan Inc) *Financial Interest www.ArcScan.com

36. METHODS: Theory of Early Keratoconus Artemis KC B-Scan Normal In early keratoconus, epithelial thinning masks the cone Earliest epithelial changes occurring in KC are detectable by Epithelial Mapping Keratoconus No Front Surface Cone Anterior stromal surface bulging Back Surface Cone

37. Are These Topographies Keratoconus? OS OD CASE 2 CASE 1 CASE 3 OD ATLAS Diagnosis

38. Results Case 1: True keratoconus Case 1 Diagnosis: KERATOCONUS OS Age 25 years Ks (D) 45.25/43.25 @ 76 Rx -1.00 -0.50 x150 BSCVA 20/16 Case 1 : NORMAL Epithelium Stroma Cornea

39. Results Case 2: False Keratoconus Case 2 : Suspect Subclinical KC OD Age 31 years Ks (D) 45.0/44.3 @ 172 Rx -5.00 -0.50 x 20 BSCVA 20/16 Higher Order Aberrations Case 2 : NORMAL Coma 3.05 µm Sph Ab 0.77 µm HO RMS 0.44 µm Epithelium Stroma Cornea

40. Case 3: Keratoconus With Normal Topography Elevation Front Pachymetry Elevation Back Elevation Front Pachymetry Elevation Back Case 3 Diagnosis: NORMAL Age 51 years Ks (D) 43.5/42.87 @ 120 (not steep) Rx -4.00 -0.50 x 35 (no cylinder) BSCVA 20/1 2.5 (no drop in BSCVA) Sagital Curvature Total Optical Power Pentacam: Progression of Corneal Thickness Orbscan Pentacam NORMAL Epithelium Stroma Cornea Keratoconus diagnosis may have been missed using surface topography screening alone Case 3 Diagnosis: KERATOCONUS

41. Are These Topographies Keratoconus? OS OD CASE 2 CASE 1 CASE 3 OD ATLAS Diagnosis Normal Keratoconus Keratoconus Final Diagnosis Including Epithelial Thickness Profile

42. Keratomileusis Early Cohort vs Modern LASIK Keratomileusis LASIK Range of myopia Up to -27.00 D 86% above -7.01 D Rarely treated above -10.00 D Screening for keratoconus None, keratoconus unknown Topography unavailable Awareness of keratoconus Astigmatism, steep & thin corneas Front & back surface topography Future advances – epithelial thickness profiles, corneal stiffness Depth of keratectomy Deep resection: 300-350 µm in all eyes Original microkeratome: inaccurate & imprecise Microkeratomes more accurate & precise Thin flaps commonly used: avg 110 µm Accurate measurement of corneal thickness and residual stromal bed Low myopia - low ablation depths Ectasia 2.8% from the original cohort ~ 0.06% (more later)

43. Microkeratome accuracy and precision

44. Thin Flap LASIK

45. Improvement in flap thickness standard deviation

46. VisuMax Femtosecond System

47. Artemis B-Scan: 6 Months Post LASIK Artemis B-Scan (above) of VisuMax Flap 6 months post LASIK. Edge detection by I-scan digital signal processing (red outline, below) based on raw scan data

48. Keratomileusis Early Cohort vs Modern LASIK Keratomileusis LASIK Range of myopia Up to -27.00 D 86% above -7.01 D Rarely treated above -10.00 D Screening for keratoconus None, keratoconus unknown Topography unavailable Awareness of keratoconus Astigmatism, steep & thin corneas Front & back surface topography Future advances – epithelial thickness profiles, corneal stiffness Depth of keratectomy Deep resection: 300-350 µm in all eyes Original microkeratome: inaccurate & imprecise Microkeratomes more accurate & precise Thin flaps commonly used: avg 110 µm Accurate measurement of corneal thickness and residual stromal bed Low myopia - low ablation depths Ectasia 2.8% from the original cohort ~ 0.06% (more later)

49. What else do we know about the long-term safety of LASIK? If ectasia were common, surgeons would know about it

55. Keratomileusis Early Cohort vs Modern LASIK Keratomileusis LASIK Range of myopia Up to -27.00 D 86% above -7.01 D Rarely treated above -10.00 D Screening for keratoconus None, keratoconus unknown Topography unavailable Awareness of keratoconus Astigmatism, steep & thin corneas Front & back surface topography Future advances – epithelial thickness profiles, corneal stiffness Depth of keratectomy Deep resection: 300-350 µm in all eyes Original microkeratome: inaccurate & imprecise Microkeratomes more accurate & precise Thin flaps commonly used: avg 110 µm Accurate measurement of corneal thickness and residual stromal bed Low myopia - low ablation depths Ectasia 2.8% from the original cohort ~ 0.06% (more later)

56. What else do we know about the long-term safety of LASIK? Ectasia in the Peer-Reviewed Literature

57. Ectasia: Peer-Reviewed Literature Is 0.12%-0.66% a realistic rate of ectasia? Report No. of Ectasia/ No. Procedures Percentage Pallikaris JCRS 2001 19/2,873 0.66% Lyle JCRS 2001 1/332 0.30% Rad JRS 2004 14/6,941 0.20% Reinstein JRS 2006 6/5,212 0.12%

60. Ectasia: Peer-Review Literature In Context

62. Ectasia: Reported Rate In Context Report No. of Ectasia/ No. Procedures Percentage Pallikaris JCRS 2001 19/2,873 0.66% Lyle JCRS 2001 1/332 0.30% Rad JRS 2004 14/6,941 0.20% Reinstein JRS 2006 6/5,212 0.12%

64. Ectasia: Reported Rate In Context Report No. of Ectasia/ No. Procedures Percentage Pallikaris JCRS 2001 19/2,873 0.66% Lyle JCRS 2001 1/332 0.30% Rad JRS 2004 14/6,941 0.20% Reinstein JRS 2006 6/5,212 0.12%

66. Ectasia: Reported Rate In Context Report No. of Ectasia/ No. Procedures Percentage Pallikaris JCRS 2001 19/2,873 0.66% Lyle JCRS 2001 1/332 0.30% Rad JRS 2004 14/6,941 0.20% Reinstein JRS 2006 6/5,212 0.12%

68. Ectasia: Reported Rate In Context Report No. of Ectasia/ No. Procedures Percentage Pallikaris JCRS 2001 19/2,873 0.66% Lyle JCRS 2001 1/332 0.30% Rad JRS 2004 14/6,941 0.20% Reinstein JRS 2006 6/5,212 0.12%

70. Subset of Population: Moria Flap Thickness

71. Subset of Population: Moria Flap Thickness Which means that 6.3% flaps will be at least 50 µm thicker than intended Intended Flap Thickness 160 µm Average Flap Thickness 163.6 µm Flap Thickness Bias +3.6 µm Flap Thickness Standard Deviation 30.3 µm

73. Probability Model for Risk of Ectasia: Microkeratomes

74. Probability Model for Risk of Ectasia: Microkeratomes 1 Million Times More Ectasia

75. Risk of Ectasia: Labeling Bias

76. Risk of Ectasia: Flap Thickness Standard Deviation

78. Lifetime Risk Factors Source: National Safety Council; http://www.nsc.org/research/odds.aspx Chance of ectasia about 1 in 2,000 One Year Odds Lifetime Odds All injury deaths 1,765 23 All accident deaths 2,794 37 Motor vehicle 6,078 80 Pedestrian 44,009 578 Fire & flames 70,913 932 Poisoning by venomous animals, plants 3,901,235 51,265 Dog bite 11,534,087 151,565 Lightning 4,210,857 55,333 Choking 82,746 1,087 Drowning in bathtub 803,891 10,564 Struck by falling object 362,410 4,762 Firearm missile 233,937 3,074 Fireworks 29,476,000 387,332 Children murdered by mothers 226,728 2,979 Children murdered by fathers 26,527,135 348,582

82. Continuing Improvements in Safety

83. Quality of Vision in Corneal Refractive Surgery Gross Safety: Loss of BSCVA

85. Myopia Safety: All Lasers DZ Reinstein

86. Hyperopia Safety: All Lasers DZ Reinstein

87. Myopia Efficacy: All Lasers DZ Reinstein Avg Max -4.02 D -13.75 D -3.98 D -14.75 D -3.78 D -9.25 D -4.54 D -12.50 D

88. Hyperopia Efficacy: All Lasers DZ Reinstein Avg Max +2.34 D +5.00 D +2.35 D +6.75 D +2.64 D +4.75 D +2.67 D +7.25 D

89. Quality of Vision in Corneal Refractive Surgery Contrast Sensitivity

90. MEL70 Myopia: Contrast Sensitivity

93. Complication Rate Experienced Surgeons

94. Complication Rate – Prof Reinstein FLAP COMPLICATIONS Eyes out of 13,148 % Lose 2 Lines Free Cap 1 (0.01%) 0.0000000% Thin Flap 2 (0.02%) 0.0000000% Incomplete Flap (no ablation) 6 (0.05%) 0.0000000% Corneal Perforation 0 (0.00%) 0.0000000% Blindness (total loss of vision) 0 (0.00%) 0.0000000% Corneal scarring reducing vision 0 (0.00%) 0.0000000% Inflammation with decrease of vision 1 (0.01%) 0.0000000% Infection 0 (0.00%) 0.0000000% Epithelial Ingrowth (requiring further surgery) 21 (0.19%) 0.0000000% Need for corneal transplantation 0 (0.00%) 0.0000000% Keratectasia 0 (0.00%) 0.0000000% LASER COMPLICATIONS Eyes out of 13,148 % Lose 2 Lines Visually sig. decentrations 0 (0.00%) 0.0000000% Laser parameter data entry error 3 (0.03%) 0.0000000%

95. What more do we know about the long-term safety of LASIK now ? More long term follow-up studies

96. Published Long-Term LASIK Outcomes - Myopia 90 eyes Mean SE: -4.85 D B&L Technolas 217 Hansatome Optical zone: 5.79 mm Stability Safety 0.0% lost 2 lines 7% lost 1 line 51% no change 42% gain 1 or more lines No ectasia 0 to -3 D -6 to -13 D -3 to -6 D All

97. Published Long-Term LASIK Outcomes - Myopia 107 eyes Mean SE: -15.71 D Summit, Technolas 116, MEL60 ACS 160 Optical zone: 6 mm Stability Safety

98. Published Long-Term LASIK Outcomes - Myopia 11 eyes Mean SE: -12.96 D MEL60 Draeger lamellar rotor keratome 150 Optical zone: 5 mm Stability Safety 0.00 -0.50 -0.96 -1.05 -1.14 -12.96

99. Published Long-Term PRK Outcomes - Hyperopia Stability Safety 40 eyes Mean SE: +4.70 D Summit Technology SVS Apex Plus Optical zone: 6 mm 5% lost 2 lines 30% lost 1 line 65% no change or improved No ectasia

100. Published Long-Term LASIK Outcomes - Hyperopia Stability Safety 47 eyes Mean SE: +3.58 D Summit Technology SVS Apex Plus Moria LSK-One 180 Optical Zone: 6 mm 0.0% lost 2 lines 2.1% lost 1 line 57.4% no change 40.5% gain 1 or more lines No ectasia

103. LASIK is safe in the long run; looking back at 50 years of lamellar corneal surgery Dan Z Reinstein MD MA(Cantab) FRCSC FRCOphth 1,2,3,4 Timothy J Archer, MA(Oxon), DipCompSci(Cantab) 1 1. London Vision Clinic, London, UK 2. St. Thomas’ Hospital - Kings College, London, UK 3. Weill Medical College of Cornell University, New York, USA 4. Centre Hospitalier National d’Ophtalmologie, (Pr. Laroche) , Paris, France Thank You