Intacs, Corneal inserts for treatment of keratoconus and ectasia

A Option for KeratoconusKeratoconus Intacs -1 Day PKP -1 Week

Contact Lens Intolerant Keratoconus Steep K ‘s, 45 to 60 Changing refractions, eyes irritated, frequent

visits/re-fits Lenses not providing functional vision

Outright failure Shortened wearing time Inability to achieve 20/40

“keratoconus personality” exacerbated Apprehensive about transplant

Active, younger or risk averse

Objective - Bridge the gap between frustration and (PKP) “the point of no

return”

Reshape the Cornea for CL Success

Oklahoma optometrist first conceptualized the idea in 1978

One of the early medical champions of contact lenses in the U.S.

Developed CorneaScope in late 1960s - led to today’s topography

Gene Reynolds, O.D.1921 - 1994

INTACS HistoryConcept for Corneal Reshaping

Arc-Shortening Model for Treating Myopia: Preoperative Representation of

the Cornea

How does it work?

Arc-Shortening Model for Treating Myopia: Representation of the Cornea

After Placement of INTACS Inserts

How does it work?

History

Adjustable Ring1984

As conceived by Dr. Reynolds

19781978 – A.E. Reynolds, O.D. conceives of – A.E. Reynolds, O.D. conceives of Intrastromal Corneal Ring (ICR)Intrastromal Corneal Ring (ICR)

19851985 - First pre-clinical studies on Dr. Reynolds' product - First pre-clinical studies on Dr. Reynolds' product

19911991 - First human clinical trials begun - Brazil - First human clinical trials begun - Brazil

1996 1996 -- U.S. myopia clinical trial begun, 150º ICRU.S. myopia clinical trial begun, 150º ICR- CE Mark approval of ICR in Europe,- CE Mark approval of ICR in Europe, -1.00 to -4.50 -1.00 to -4.50

DD

19971997 - Joseph Colin, MD inserts first ICR for Keratoconus - Joseph Colin, MD inserts first ICR for Keratoconus

Milestones

INTACS Design Features Precision manufactured

to ± 0.01mm: •150° arcs PMMA•Unique hexagonal cross-

section design with 7mm wide optical zone

•Positioning holes for manipulation

Inserts placement:•In peripheral cornea•Between stromal layers

Stromal Lamellae

6.9 mm

8.1 mm

Stromal Lamellae

How INTACS Work…

Inserts placed at 75% corneal depth

Inserts separate corneal lamellae

Separation shortens corneal arc length

Central cornea flattens Increased flattening

achieved with thicker segments

1999 - FDA approval for myopia, -1.00 to -3.00 D

2001 - Addition Technology purchased INTACS technology to pursue keratoconus indication

2003 - CE approval granted for keratoconus in Europe

2004 - FDA approval for keratoconus under Humanitarian Device Exemption (HDE)

2005 – Over 5000 INTACS corneal implants procedures for keratoconus performed worldwide

Milestones cont’d

Keratoconus

Non-Inflammatory Ectasia• Stromal Thinning• Disruption of Bowman’s

Membrane

Corneal Ectasia• Myopia• Irregular Astigmatism

Optical Correction• Spectacles– early• Contact Lenses– later

Keratoconus

Demographics•Estimates vary from 50

to 170 per 100,000

Obscure Etiology•Heredity•Allergies, Eye Rubbing

Why Does the Cornea Bulge in Keratoconus?

Corneal tissue is abnormal• Too elastic?• Abnormal cross-linking of

collagen?

Loss of structural integrity of Bowman’s Layer?

Keratocyte apoptosis• Trauma (eye rubbing)

Corneal tissue bulges because it is too thin?

Current Surgical Options - Keratoconus

10% to 20% of Keratoconus Patients Ultimately Require Surgery

Lamellar Keratoplasty• Interface haze limits visual result

Penetrating Keratoplasty• Most frequent procedure – 4,771 cases in 2004 (US)• 80-90% successful• Issues

Graft rejection rate 17.9% Continued astigmatism Endothelial cell loss (limited longevity of graft) Recurrence of Keratoconus

INTACS… a New Surgical Option

Goal is to restore functional vision

•Effective functional refraction with soft, soft-toric, or rigid contact lenses

•Create cornea more receptive to contact lenses

INTACS Normalize Corneal Shape

The INTACS Procedure

Courtesy David Schanzlin, MD Shiley Eye Inst. UCSD

Pre-Op UCVA 20/200 MR: -4.75 + 5.25 X 005 = 20/40 RGP intolerant

Post-Op (Day 1)

UCVA 20/50++ MR: -1.00 + 2.75 X 150 = 20/20 Soft Toric

Courtesy David Schanzlin, MD Shiley Eye Inst. UCSD

Procedure Outcome

“ Fitting CL’s on keratoconus patients who have INTACS is feasible and has a role in augmenting

their vision” Nepomuceno, Boxer Wachler, Weissman, CLAE 2003 175-180

pre-op BCVA post-op BCVA post-op BCLVA Lens

31 F 20/32 20/25 20/16 soft toric

44 M 20/125 20/50 20/25 cust. RGP

34 M 20/63 20/40 20/20 cust. RGP

All were CF UCVA pre-op and 20/200 or better post-op

INTACS Case FilesPre-Op

UCVA CF BCVA: 20/50 MR: -7.00 -6.00 @ 60 Max K: 46.60 @ 175 Custom RGP Intolerant

Case 1

Anterior Posterior

INTACS Case Files

UCVA 20/80 BCVA: 20/30 MR: -2.00 -2.75 @ 60 Max K: 43.40 @ 14 Soft Toric

Case 1Post-Op Anterior Posterior

Architecture Modification

Architecture Modification

Pentacam Images

INTACS Case Files

UCVA CF BCVA: 20/50 MR: -4.75 + 5.00 @ 20 Max K: 55.78 @ 90 Custom RGP Intolerant

Case 2OD Pre-OP

INTACS Case Files

UCVA 20/40 BCVA: 20/25 MR: -2.00 Max K: 51.69 @ 89 RGP Tolerant

Case 2OD Post-OP

INTACS Optics

Maintains prolate cornea

Enhances structural integrity (second limbus)

Additive – Removable - Replaceable

Large, clear central optical zone

INTACS & The Prolate CorneaINTACS LASIKNormal

Cornea

In vivo Hartman-Shack analysis

Peer Reviewed Literature INTACS for Keratoconus

Primary Auth. Title Eyes

Levinger Keratoconus Managed with Intacs, Arch Ophthal, Oct 05 53

Uusitalo Treating Keratoconus with Intacs, JRS May 05 50

Alio One or Two Intacs for correction of Keratoconus, JCRS May 05 26

Colin Current Surgical Options for Keratoconus, JCRS Feb 03 0

Tunc Intacs for Asymetrical Astigmatism of Keratoconus, Journal of French Ophthal. Oct 03 9

Boxer Wachler Intacs for Keratoconus, Ophthalmology May 03 74

Colin Intacs and Refractive IOL to Correct Keratoconus, JCRS Apr 03 1

Siganos Management of Keratoconus With Intacs, AJO Jan 03 33

Colin Intacs for Treating Keratoconus, Ophthalmology Aug 01 10

Colin Utilization of Refractive Technology in Keratoconus and Transplants, Cur Opin Ophthal 2002 0

AlioChanges in Keratoconic Corneas after Intacs Expantation and Reimplantation, Opthalmology Apr

04 5

Lemp Intacs Safety in Keratoconic Eyes, Invest Ophthalmol Vis Sci ARVO 04 164

Colin Correcting Keratoconus with Intracorneal Rings, JCRS Aug 00 10

Guell Are Intacs Usefull in Refractive Surgery, Curr Opinion Ophthal. 2005 222

Weissman Feasibility of Contact Lens Fitting on Keratoconus Patients with Intacs, CLAE 2003 3

Total Eyes Summarized 660

Unique Eyes Summarized 338

INTACS Clinical Overview First case 1997: Joseph Colin, MD

•Decentered Cone

•Segment Placement Superior thin segment : 0.25 mm Inferior thick segment : 0.45 mm

•Very encouraging results Patient scheduled for immediate PKP, Transplant has been deferred 7+ years with acceptable

BSCVA Reduction in myopia and astigmatism Results stable over time

Combined Studies 1997- 2003

Colin (2001) – 10 eyes • Ophthalmology 2001; 108:1409-1414.

Siganos (2003) – 33 eyes • American Journal of Ophthalmology 2003; 135:1:64-70.

Boxer-Wachler (2003) – 74 Eyes• Ophthalmology. 2003; 110:1031-1040.

European Clinical (2003) – 34 eyes • Accepted for Publication Ophthalmology

Combined Studies 1997- 2003

Change UCVA

0%

20%

40%

60%

80%

100%

Gain 2 or More Lines

No Change +/- 1 Line

Loss 2 orMore Lines

European Study Siganos Boxer Wachler

78%

22%

0%

67% 72%

33%

19%

9%0%

Combined Studies 1997 - 2003 Change BSCVA

0%

20%

40%

60%

80%

100%

Gain 2 or More Lines

No Change +/- 1 Line

Loss 2 orMore Lines

European Study Siganos Boxer Wachler

62%

32%

6%

45%45%52%

51%

4%3%

CL Intolerant - Pre-Op BCVA Achieved to Complete Exam

Combined Studies 1997 - 2003 Follow-up shows stable and lasting effect

Very Few Surgical Complications Observed

Postoperative Complications• Superficial placement • Segment migration• Visual symptoms• Lack of effect

Manageable with INTACS Removal• 14/174 eyes (8%)• Majority of patients returned to preoperative refraction upon

removal• Several have gone on to have successful corneal transplantation

European Keratoconus Study Results Summary

Dr. Joseph Colin (France) pioneered the use of INTACS in Keratoconus

First case in 1997

7 years follow up with stable results

Very few INTACS patients have required corneal transplants in 7 years

In the few cases where PKP was performed, no problems were reported

European Keratoconus Study

Change in MRSE• Mean - 3.1 Diopters Corrected• Range -1.6 to 8.7 Diopters

Change in Cylinder• Mean - 2.9 Diopters Corrected• Range - 0 to 7.5 Diopters

Stability of refraction achieved at 3 to 6 months

• 75% within ± 1 Diopter• 50% within ± 0.5 Diopter

European Keratoconus Study2 year data - Joseph Colin, MD*

96 of 100 eyes, initially referred for PKP, successfully implanted with INTACS and remain stable after 24 months

100% became contact lens tolerant, some patients became correctable with spectacles and a subset required no correction

80% have improved UCVA and 68% improved BCVA at year 2

Manifest refraction, cylinder, MRSE and pachymetry continued to improve at year 2 over year 1 and preoperative exams

* Accepted for Publication JCRS

INTACS – PKP Comparison

+8.00 (.)-2.00 X 180°-0.75TransplantIntacs

INTACS - PKP ComparisonPKP

Irreversible Procedure Time: 1 Hour Rehab Time: Immed-

18 MonthsIntraocular Procedure Complications

• Cataract• Glaucoma• Endophthalmitis• Rejection• Expulsive hemorrhage• Neovascularization• Induced astigmatism• Disease recurrence• Risk of viral transference

INTACS Reversible Out-Patient

Procedure Time: 20-30 Minutes Rehab Time: 1-2 Weeks

(Visual Function Immediate) Corneal Lamellar Procedure Periodic Follow-up Complications

• Unsatisfactory ring placement• Segment extrusion(All easily managed with segment removal))

INTACS - PKP ComparisonPKP

Significant loss of endothelial cells

Permanently weakened cornea with risk of additional trauma

Outcomes: unpredictable, often unstable

INTACS

Endothelial cell loss, not clinically significant1

Provides structural integrity, PKP still an option without complication

Outcomes: predictable, case dependent

1Two-Year Endothelial Cell Assessment following INTACS implantation, Azar et al, J Refract Surg. 2001 Sept-Oct

Conclusions: INTACS Intervention is a good

alternative to Transplant Goal of INTACS is to restore functional vision

• Effective functional refraction with soft, soft-toric, or rigid contact lenses is likely

• Creates cornea more receptive to contact lenses

INTACS implantation reduces corneal coning• Central cone is flattened• Asymmetrical cones are repositioned centrally

Post-surgical recovery• Visual improvement can be immediate • Vision stabilizes in months rather than a year or longer

High potential to defer transplant

INTACS Case Files

UCVA CF BCVA: 20/45 MR: -6.25 -4.75 @ 175 Max K: 54.43 @ 79 Custom RGP Intolerant

Case 3OS Pre-Op

INTACS Case Files

UCVA 20/80 BCVA: 20/30 MR: -.50 -3.00 @ 135 Max K: 51.69 @ 89 RGP Tolerant

Case 3OS Post-Op

INTACS Removal & Replacement Summary

Easy to remove

In FDA study, no complications post-removal

Preliminary data indicates that the patients return to their preoperative refractive error in most cases

Patients are able to return to their original mode of correction or to pursue an alternative refractive procedure

Keratoconus Treatment Flow The Old Paradigm

Disease Identification &

ManagementSpectacles, Contacts,

Custom Lenses

Optometric Physician

Identification of Surgical Need

Contact Lens Intolerance or

Central Scarring

Optometric Physician

Work-Up, PKP Surgery, Post-Op1 to 3 Months Patient

Recovery

Surgeon

PKP Post-OpCare

12 to 24 Months

Optometric Physician

Post PKP Fitting Specialty Custom Lenses

Optometric Physician

Long-Term Follow-Up

Specialty CL Fitting, Regular Monitoring (Re-Graft 17.9%)

Optometric Physician

Keratoconus Treatment Flow The New Paradigm

Disease Identification &

ManagementSpectacles, Contacts,

Custom Lenses

Optometric Physician

Identification of Surgical Need

Contact Lens Intolerance or Risk

of Scarring

Optometric Physician

Work-Up, INTACS Surgery, 1-Day & 3-Month Post-Op

1-2 Days Patient Recovery

Surgeon

Ongoing Follow-Up

Include Initial CL Fit

Optometric Physician

Post-Op Management &

Outcome AnalysisRe-Referral if

Complications or Atypical Outcomes

Optometric Physician

Long-Term Follow-Up

Include CL Fitting, Periodic Monitoring

(Defer PKP)

Optometric Physician

Contact lens intolerant keratoconus

Improve contact lens success, UCVA, BCVA

Defer PKP and associated risks

Keep on the conservative side of leading edge patient care technology

Retain patient loyalty and follow-up care

Why recommend INTACS ?

Contact Lens Intolerant Keratoconus

K readings 45 to 60

Contact lenses not providing functional vision Outright failure Shortened wearing time Inability to achieve 20/40 Desire to forestall central scarring

Apprehensive about transplant

Or, if Surgical Intervention is Medically Necessary

Ideal INTACS Patients

Those who strongly desire refractive surgery, but work-up exhibits concerning signs

Posterior anomaly Forme fruste keratoconus or pellucid-like

topography

Those who desire refractive surgery, but fear “no-return” of laser ablation

Wish to retain options for future conditions or technologies

Advanced, Additive, Removable Up to -3.00D sphere and 1.00D astigmatism

INTACS a refractive option for …