This document discusses Avedro's corneal cross-linking technology for treating keratoconus and ectasia. It summarizes that in February 2015 an FDA advisory committee voted to approve Avedro's application, but in March 2015 the FDA requested additional information. It then provides several case studies demonstrating the effectiveness of Avedro's Photorefractive Intrastromal Cross-Linking (PiXL) technique for keratoconus, post-LASIK ectasia, post-cataract myopia, and refractive enhancement post PRK or for hyperopia correction.

1. The Worldwide Leader in Corneal Cross-Linking Science &
Technology

2. On February 24, 2015:
US FDA Dermatologic and Ophthalmic Drugs
Advisory Committee and Ophthalmic Devices
Panel of the Medical Devices Advisory
Committee voted in support of approval for
Avedro’s NDA for riboflavin ophthalmic solutions
with UVA irradiation for use in corneal cross-
linking for the treatment of progressive
keratoconus or corneal ectasia
United States FDA Update
Cross-linking for Keratoconus & Post-LASIK Ectasia

3. On March 29, 2015:
A complete response letter from the U.S.
FDA regarding the NDA was received.
Additional information was requested in
areas of the application concerning the
device, which Avedro believes it can
provide.
United States FDA Update
Cross-linking for Keratoconus & Post-LASIK Ectasia

4. Lasik Xtra

5. Standard 9mm Cone-localized
Roy & Dupps, IOVS 2011
PiXL: Photorefractive Intrastromal Cross-Linking
A.S. Roy & W.J. Dupps, Jr.
Patient Specific Computational Modeling of
Keratoconus Progression and Differential
Responses to Collagen Cross-linking
IOVS Nov 2011, 52:12
Finite Element Analysis

6. 15 J/cm2
10 J/cm2
5.4 J/cm2
3 Month Post-OP Pre-OP Difference
Professor Anders Behndig

7. PiXL for Irregular Corneas: Case Example
60 Y.O. male with
paracentral steep
zone
Preop:
BCVA: 20/50
1 Week Post-OP
BCVA: 20/25
UCVA: 20/25
Case from Prof. H.Burkhard Dick

8. Immediate Pre-Operative 1 Month Postoperative 17 Months Postoperative
Longest PiXL Follow-Up
Case from: Dr. A.John Kanellopoulos

9. Pre-OP
Refraction: -2.50 D
BCVA: 20/20, UCVA: 20/50
3 Month Post-OP
Refraction: -0.75-0.25x 177
BCVA: 20/20, UCVA: 20/25
Baseline Topography Post-Op Topography
ComputerSimulationActualPentacam
Pentacam Difference Map
Predictive Finite
Element Analysis
Modeling
vs.
Actual Clinical
Outcomes
Clinical case from Prof. H.Burkhard Dick

10. PiXL For Post-Cataract Myopia Case Example: 9 Month Post-op
9 Months Pre-OP
Case from: Dr. Pavel Stodulka
52 year old Female
Pseudophakia OD
Pre-OP:
-1.25 -0.25 x 180
BCVA 20/20
UCVA 20/200
9 Months Post-OP:
-0.50 sphere
BCVA: 20/20
UCVA: 20/25

11. 9 Months Post 3 Months Post
Case from: Dr. Pavel Stodulka
PiXL For Post-Cataract Myopia Case Example: Stability from 3- 0 Months

12. Transepithelial PiXL
Refractive Enhancement Post PRK
Post-PRK, Pre-PiXL
UCVA: 20/50
BCVA: 20/20
Manifest Refraction: -1.00 Sphere
3 Months Post-PiXL
UCVA: 20/20
BCVA: 20/20
Manifest Refraction: Plano
Case from Dr. Roberto Pinelli

13. Transepithelial PiXL for Hyperopia
Post Pseudophakic IOL
Post-IOL, Pre-PiXL
UCVA: 20/25
BCVA: 20/20
Manifest Refraction: +0.75+0.25x180
3 Months Post-PiXL
UCVA: 20/20
BCVA: 20/20
Manifest Refraction: Plano
Case from Dr. Roberto Pinelli