Northern Colorado Eye Center Continuing Education Event Corneal Collagen Cross-linking September 20, 2014 S. Lance Forstot, MD, FACS Corneal Consultants of Colorado Founding Partner Clinical Professor of Ophthalmology University of Colorado Medical School

Corneal Collagen Cross-linking September 20, 2014 S. Lance Forstot, MD, FACS Corneal Consultants of Colorado Founding Partner Clinical Professor of Ophthalmology University of Colorado Medical School

Ultraviolet Light UVC – nm –Blocked by ozone layer UVB – nm UVA – nm

Ultraviolet Light UVA –Can induce corneal endothelial damage with surface dose of 42.5 J/cm 2 –Typical dose for CXL only 5.4 J/cm 2 –Estimated dose received by cornea in min of sun exposure on a summer day

All Exposed Tissues:  Spring J/cm 2 /day in 3-4 hrs outdoors  Fall ~60J/cm 2 /day of solar UVA Cornea:  5J/cm 2 in min in Summer Real World UV Hawaii in Spring Australia in Summer

3.00 mW/cm² 1.49 mW/cm² 0.74 mW/cm² 0.36 mW/cm² 0.18 mW/cm² 0.09mW/cm² 0.06 mW/cm ² 0μm 100μm 200μm 300μm 400μm 500μm 600μm 100% 50% 25% 12% 6% 3% 2% Endothelium Damage threshold 3.00 mW/cm² Safety of Cross-Linking

How much UV – light gets into the eye ? Radiant Energy is Below Damage Threshold

Safety of UVA-Riboflavin Cross-Linking of the Cornea Min pach of 400 μm protects endothelium, lens, retina Spoerl, et. al Cornea 2007; 26: µ

Riboflavin (Vitamin B2) Critical role in CXL Increases UVA absorption to 95% in saturated corneas (versus 32% w/o)

Riboflavin

Diabetics, KCN and CXL Diabetics don’t often develop adv KCN because of natural cross-linking from sugars and UV light Seiler T, Huhle S, Spoerl E, Manifest Diabetes and Keratoconus, Graefe’s Arch 2000

CXL – UVA+Riboflavin Results in increase in biomechanical rigidity (stiffening) Strongest effect in anterior 300u –Which plays major role in maintaining corneal curvature Results in corneal flattening and and reduction in spherical equivalent

CXL with Riboflavin ↑Rigidity In Europe since 1998 New Tx in US KCN, pellucid, ectasia, post-RK Scanning Electron Microscopy Stiffened Cornea Normal Cornea

CXL Mechanism –Not completely understood –Riboflavin known to generate active oxygen species (singlet oxygen and superoxide anion radicals)

Pre op 6 m postop 3 m postop1 m postop Apoptosis 300 μm deep after CXL Repopulation takes 6 months Courtesy of Dr. Caporossi, Confocal Microscopy

Crosslinks Between Collagen Fibers Strengthens Cornea like Ladder Rungs

Cross-Linking is Not New Hardening of polymers in materials science since 1930s (silicone oil→rubber ball) Dentists XL for decades Normal aging of connective tissue involves cross-linking and stiffening KCN progression ↓ with age

We All “Crosslink” as we Grow Up

History of CXL Basic research by Seiler & Spoerl First patients Txd in 1999 Today over 400 centers worldwide Standard of care for KCN (in Europe as young as 9)

CXL Technique Anesthetic drops, painless Prepare cornea Riboflavin drops for 30 mins UV light for 30 mins Bandage contact lens

Riboflavin 0.1% Drops

Patient’s View of UV Light

UV-A Light

CXL & Curvature Change Change in avg or steep K does not provide key info See diff maps to appreciate true curvature changes

PreopPostop 11 M Difference Map 5 D Steeper 3 D Flatter

Preop 6 M Postop 9 M Postop 12 M Postop 429 um 450 um 411 um ( 8.6%) 450 um Pachymetry Maps

Pre Op 6 months Post Op UCVACF100 BSCVA2520 Refraction x x yr old male with Keratoconus: Epi-On CXL OS 6 monthsPreop Difference Map William Trattler, MD case

CXL: Epi-On v. Epi-Off

Post Op 3 Months Pre OpDifference Map ODUCVARefractionBSCVA Pre Op x Months x17525 Epi-On Crosslinking for Ectasia 38 year-old male with post-Lasik ectasia William Trattler, MD case

BSCVA Comparison

Summary of Epi-ON EPI-On CXL –Benefits: Faster visual recovery/less pain Reduced risk of pain/haze Very good clinical results –Even in keratoconus patients over the age of 35 –Downside: Longer procedure (30-50 min longer) Can not combine with simultaneous topo-guided PRK William Trattler, MD

Final Points Epi-On can be as effective as Epi-Off –Technique differences can explain differences in results Age is not a major factor –Older patients can benefit from crosslinking Progression is not required for successful results with crosslinking –Non-progressive patients can achieve improvement in corneal shape, UCVA, and BSCVA

Long-term Results 241 eyes Follow-up 6 months to 6 years Flattening: 2.68 D at 1 year; 4.84D at 3 years BCVA improvement (> 1 line): 53% at 1 year No BCVA lines lost 2 patients had KCN prog and repeat CXL (Also AJO April 2010) Raiskup-Wolf, Hoyer, Spoerl. J Cat Ref Surg May 2008

Long Term Results  5 year study, 48 eyes (60 pts treated)  No patient had prog of keratectasia.  Postop avg improvement 2.87 D  Improvement in BCSVA by 1.4 lines Wollensak G. Crosslinking treatment of progressive keratoconus: New hope. Curr Opin Ophthalmol Aug;17:356-60

CXL for KCN, Ectasia Shown safe and effective worldwide Arrests KCN progression (95+%) UCV, BCSVA, CL tolerance ↑ (60-80%) Ideal candidates ≤ 45 y/o, corneal thickness ≥ 400 µm, limited scarring Minimum age in Europe now 9 y/o

CXL Complications Infectious keratitis – bacterial, fungal Sterile ulceration Corneal haze HSV keratitis Corneal edema

Ring segments PRK Topo-guided PRK Better PKP Results? After CXL

Topographically-Guided Ablation  Developed by Theo Seiler  Over 22,000 curvature points on the cornea  Linked to excimer laser  Main indications irreg astig, decentered ablations, small OZ

Topography Ablation More tissue removed

CXL Other Applications –Corneal edema –Infectious Keratitis –Radial Keratotomy

CXL and Ortho-K

CXL and the FDA Current status -Investigational Physician IND IRB Trials FDA Trials

Thank you for your attention

S. Lance Forstot, MD, FACS www. corneacolorado.com