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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. Ultraviolet Light. UVC 220-290nm
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Northern Colorado Eye CenterContinuing Education EventCorneal Collagen Cross-linkingSeptember 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 • 220-290nm • Blocked by ozone layer • UVB • 290-320nm • UVA • 320-340nm
Ultraviolet Light • UVA • Can induce corneal endothelial damage with surface dose of 42.5 J/cm2 • Typical dose for CXL only 5.4 J/cm2 • Estimated dose received by cornea in 15-20 min of sun exposure on a summer day
Real World UV Hawaii in Spring Australia in Summer All Exposed Tissues: • Spring 170-200J/cm2/day in 3-4 hrs outdoors • Fall ~60J/cm2/day of solar UVA Cornea: • 5J/cm2 in 15-20 min in Summer
3.00 mW/cm² Safety of Cross-Linking Endothelium Damage threshold 0μm 100μm 200μm 300μm 400μm 500μm 600μm 100% 50% 25% 12% 6% 3% 2% 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/cm²
How much UV – light gets into the eye ? Radiant Energy is Below Damage Threshold
300 µ Safety of UVA-Riboflavin Cross-Linking of the Cornea Min pach of 400 μm protects endothelium, lens, retina Spoerl, et. al Cornea 2007; 26:385-389
Riboflavin (Vitamin B2) • Critical role in CXL • Increases UVA absorption to 95% in saturated corneas (versus 32% w/o)
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 Stiffened Cornea Normal Cornea Scanning Electron Microscopy
CXL • Mechanism • Not completely understood • Riboflavin known to generate active oxygen species (singlet oxygen and superoxide anion radicals)
Confocal Microscopy Pre op 1 m postop 3 m postop • Apoptosis 300 μm deep after CXL • Repopulation takes 6 months Courtesy of Dr. Caporossi, 6 m postop
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
History of CXL • Basic research 1993-97 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
CXL & Curvature Change Change in avg or steep K does not provide key info See diff maps to appreciate true curvature changes
Preop Postop 11 M Difference Map 5 D Steeper 3 D Flatter
Preop 6 M Postop 450 um 411 um ( 8.6%) Pachymetry Maps 9 M Postop 12 M Postop 429 um 450 um
56 yr old male with Keratoconus: Epi-On CXL OS Difference Map 6 months Preop William Trattler, MD case
Epi-On Crosslinking for Ectasia 38 year-old male with post-Lasik ectasia Post Op 3 MonthsPre OpDifference Map William Trattler, MD case
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. 2006 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
After CXL • Ring segments • PRK • Topo-guided PRK • Better PKP Results?
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 the FDA • Current status -Investigational • Physician IND • IRB Trials • FDA Trials
S. Lance Forstot, MD, FACS • www. corneacolorado.com • SL4STOT@aol.com