The document summarizes updates on corneal cross-linking (CXL) technology from Avedro, including: 1) In March 2015, Avedro received a letter from the FDA requesting further information about equivalency between study devices and commercial systems for CXL to treat keratoconus and ectasia. 2) Agreement was reached on additional measurements required to address the FDA's questions. The application was resubmitted in October 2015. 3) Preliminary data is presented on trials of a new CXL technique called PiXL for treating myopia, keratoconus, and post-cataract refractive error, showing safety and efficacy.

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

2. United States FDA Update
Cross-linking for Keratoconus & Post-LASIK Ectasia
• On March 29, 2015, Avedro received a Complete Response
Letter (CRL) to its NDA for riboflavin ophthalmic solutions with
UVA irradiation for use in corneal cross-linking for the treatment
of progressive keratoconus or corneal ectasia.
• The questions raised by the CRL were related to equivalency
between the study device and final commercial system.
• Agreement reached on specific measurements required to
address these questions. Application resubmitted October 16,
2015.
• PDUFA date 6 months from resubmission date.

3. PiXL: Photorefractive Intrastromal Cross-linking

4. 2.5 mm
3 mm
4mm
6 mm
-0.89 D
+ induced
abberations
Pre-Op
Simulation using patient baseline data
Effect of treatment zone size
1.5 X Stiffening factor
Refractive Cross-linking:
Finite Element Modeling
Cleveland Clinic Research Group
William J. Dupps, Jr., MD, PhD
-0.37 D
-0.38 D
-0.90 D

5. PiXL
Treatments
Worldwide
Aldo Caporossi
Anders Behndig
Andrew Logan
Cosimo Mazzotta
Cristhian Sancho
David Donate
Federico Alonso
Francois Malecaze
Imran Rahman
Julien Theng
Luigi Fontana
Michael O'Keefe
Mitsutoshi Ito
Paul Hughes
Pavel Stodulka
Prof. Zhou
Rick Wolfe
Roberto Pinelli
Rohit Shetty
Sylvia Paulig
Theo Seiler
Vicente Rodriguez

6. 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

7. Preliminary Data
Error bars are standard errror of the mean
# Eyes Baseline 1 month 3 month 6 month 12 month
15 J 12 12 12 9 7
10 J 18 18 14 10 2
Prospective Clinical Trial of PiXL for Myopia: Efficacy

8. Prospective Clinical Trial of PiXL for Myopia: Safety
Preliminary Data
Error bars are standard errror of the mean
# Eyes Baseline 1 month 3 month 6 month 12 month
15 J 12 12 12 9 7
10 J 18 18 14 10 2

9. 12 Month Stability (n=9)
Prospective Clinical Trial of PiXL for Myopia
Patient IK:
Change
from
Baseline
Patient IK:
Stability:
from
3 to 6
Months

10. Post-Op Pre-Op Difference
12 Month Visual Outcome: 38 Year Old Myope
Pre-OP:
-1.75-0.75x175
UCVA: 20/50
BCVA: 20/20
3 Month Post-Op:
-0.25-0.25x160
UCVA: 20/20
BCVA: 20/20
6 Months Post-OP:
-0.25-0.50x160
UCVA: 20/25
BCVA: 20/20
12 Months Post-OP:
-0.25 -0.50x180
UCVA: 20/20
BCVA: 20/20
Case from: Prof. Dr. Burkhard Dick

11. Post-Cataract Myopia Case Example
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

12. 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

13. PiXL Clinical Outcomes
• No significant adverse events to date
• Gentle procedure with no tissue removal
• No persistant postoperative glare, haloes, or dry eye
symptoms
“It’s funny how patients who might be good PiXL candidates seem to
be popping out of the woodwork – real field of dreams stuff.”
Dr. Andrew Logan
“Reviewed PiXL today... surgeon and patient ecstatic."
Dr. Paul Hughes
“I am very very very very happy, I just saw my first patient of bilateral
Pixl [for myopia]. She is great and very happy with [her] UCVA”
Dr. Vicente Rodriguez

14. www.cxl-congress.com
Thank You