Northern Colorado Eye CenterContinuing Education Event

Corneal Collagen Cross-linkingSeptember 20, 2014

S. Lance Forstot, MD, FACSCorneal Consultants of Colorado

Founding PartnerClinical 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

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

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/cm²

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 ?

0.65 J/cm2

70 J/cm2

70 J/cm2 7.7 J/cm2

Damage thresholds

0.46 J/cm2 (9 %)

0.33 J/cm2 (7 %)

0.14 J/cm2 (2.1%)

0.12 J/cm2 (1.9%)

Radiant exposures

5.4

J/cm

2

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, Spoerl, et. al Cornea 2007; 26:385-389et. al Cornea 2007; 26:385-389

300 300 µµ

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

lightSeiler 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 MicroscopyConfocal 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 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

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

Preop Postop 11 M

Difference Map

5 D Steeper3 D

Flatter

PreopPreop 6 M Postop

9 M Postop 12 M Postop12 M Postop

429 um

450 um 411 um ( 8.6%)

450 um

Pachymetry Maps

Pre Op 6 months Post Op

UCVA CF 100

BSCVA 25 20

Refraction -7.75+0.75x150 -3.75 +1.50 x 180

56 yr old male with Keratoconus: Epi-On CXL OS

6 months Preop Difference MapWilliam Trattler, MD case

CXL: Epi-On v. Epi-Off

Post Op 3 Months Pre Op Difference Map

OD UCVA Refraction BSCVA

Pre Op 200 -3.50+6.50x180 30

3 Months 50 -0.75+1.75x175 25

Epi-On Crosslinking for Ectasia38 year-old male with post-Lasik ectasia

William Trattler, MD case

BSCVA Comparison

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. 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

• 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

• SL4STOT@aol.com