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6/23/2017
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CXL
Derek N. Cunningham, O.D., FAAO
6/23/2017
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Disclosure
• In the last 12 month I have had relations with the following companies:
• Abbott
• Alcon
• Allergan
• B+L
• Reichert
• Arctic Dx
• Tearlab
• Avedro
• Innovision
• TearScience
• Lumenis
background
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Keratoconus basics
• Collagen fibers are highly uniform in diameter (25‐35 nm)
• The distance between two corneal fibers is also highly uniform (41.5nm)
Keratoconus and Post‐LASIK ectasia
Keratoconus:
• Non‐inflammatory, degenerative disorder of the cornea characterized by progressive ectasia and stromal thinning.
• Reported prevalence of 1 in 2000 in the general population.[1]
Post‐LASIK corneal ectasia:
• Corneal weakening after a LASIK procedure, creating progressivesteepening and thinning of the cornea and loss of BSCVA.
• Incidence of post‐LASIK ectasia estimated to be 1 in 1000 cases ofLASIK surgery.
[1] Feder RS, Kshettry P. Non‐inflammatory ectatic disorders. [book auth.] Mannis MJ, Holland EJ, eds Krachmer JH. Cornea. Philadelphia : Elsevier Mosby, 2005:956, Vol. Chapter 78.
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Typical Cone
Cone?28 y/o female – 10 year dx of KC
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Cone?28 y/o female – 10 year dx of KC
41 y/o female – 20 year dx KC
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41 y/o female – 20 year dx KC
Newly Diagnose Keratoconic25 y/o white female
• Upset with the sudden diagnosis
• Very upset with the contact lens cost
• Went on line and did DAYS of research
• Came to us for crosslinking (was not told about crosslinking)
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Referring Docs Scans
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Other Options?
A.Try a different less expensive lens
C. Corneal Transplant
A.Try a different less expensive lens
C. Corneal Transplant
• B. Crosslink
• D. Monitor
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One week later
Lotemax QIDRestasis BIDOmega 3 supplements
1 week later
6 Months later
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First, Fix the Surface…
• Better pre-op data, better quality post-op
– Artificial Tears. All pts.
– O-3 FA. Almost all pts.
– Topical Cyclosporin.
– Topical Azithromycin
– Topical steroids
– Plugs.
Ectasia
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CXL ‐ Basics
Basics
• Soaking the cornea with riboflavin (vitamin B2) and then exposing the cornea to ultraviolet (UV) light with a 370‐nm wavelength at 15 ‐ 45 mW/cm2.
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Riboflavin (vitamin B2)
• Water soluble, not stored
• Helps metabolism of carbs, fat and protein
• Important for skin, hair, eyes, and liver
• RDA = 1.5mg/day
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UV absorbtion
Cross‐linking
Corneal collagen cross‐linking
The figures above show the parallel corneal layers (white) and the collagen cross‐linking (red) which are increased after Corneal Cross‐Linking treatment.
Cross‐Linking:
• Improves the biomechanical properties of the cornea by strengthening the corneal tissue in the anterior stroma.
• The only procedure available to specifically stop the progression of keratoconus and strengthen the individual collagen fibers in the cornea.
• Corneal cross‐linking (also know as CXL) is a procedure that has been in global clinical use since 1997.
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Cross‐linking – First Procedures
Standard CXL, developed by Eberhard Spoerl and Theo Seiler in 1997.[2]
CXL procedure includes:
• Removal of corneal epithelium and then pre‐treating with riboflavin0.1% ophthalmic solution (0.1% diluted in 20% Dextran) for 30minutes.
• Cornea then irradiated with 3 mW/cm2 of UVA (365 nm) for 30minutes delivering a total radiant exposure of 5.4 J/cm2.
Exposure of cornea to the combination of UVA light with riboflavinphotosensitizer induces cross‐linking of the corneal collagen fibrils with aresultant increase in tensile strength and diameter of the collagen fibrils.
[2] Conservative therapy of keratoconus by enhancement of collagen cross‐links. Seiler T, Spoerl E, Huhle M, Kamouna A. s.l. : Invest. Ophthalmol. Vis. Sci., Vol. 37. S1017.
Result
• STIFF OLD
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Risks
• Pain
• Blurred vision
• Delayed healing
• Infection
• Inflammation
• Corneal haze
• Dry eye
Method
• Remove cornea
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Video
Avedro’s Cross‐Linking Products
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C
• CE Marked • FDA Orphan Drug Designation
RFID Card & RiboflavinRFID Card & Riboflavin
KXLTM SystemKXLTM System
© 2012 Avedro
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Avedro’s KXL System
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
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Post op
• Handle like a surface ablation patient
• Steroid, antibiotic, NSAID
• Bandage lens for 1 week
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Clinical Course
• Gets worse initially
Method
• Epithelium on?
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5 minutes post “disruption”
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1 day p/o
1 day p/o
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1 day p/o
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ACOS‐KXL‐001:
Cross‐linking Trial in Patients with Keratoconus or Corneal Ectasia following Refractive Surgery
© 2012 Avedro The VibeX™ / KXL™ System is not approved for sale in the United States MA‐000178 Rev. C
Overall Study Design
Sponsor: ACOS
Title: A Multi-Center, Randomized, Controlled Evaluation of the Safety and Efficacy ofthe KXL System with VibeX (Riboflavin Ophthalmic Solution) for Corneal CollagenCross-Linking in Eyes with Keratoconus or Corneal Ectasia after Refractive Surgery
Phase: III
Planned Sample Size: up to 2000 primary eyes with keratoconus and up to 2000primary eyes with corneal ectasia at 100 sites randomized in 1:1:1 ratio between 3active treatment groups.
Primary Efficacy Criteria: Mean change in maximum corneal curvature (Kmax) frombaseline to 6 months or from baseline to 12 months (within subject comparison). Eachtreatment condition (keratoconus and corneal ectasia) and treatment group will beevaluated independently.
Schedule of Assessments: Screening/baseline, Day 0 (randomization/treatment day), 1 day, 1 week, and 1, 3, 6 and 12 months after treatment.
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
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Inclusion Criteria
Presence of central or inferior steepening on the topographic map
BSCVA better than 1 and worse than 80 letters on the Early Treatment of Diabetic Retinopathy Study [ETDRS] chart
At least 12 years of age
For corneal ectasia patients only: • Diagnosis of corneal ectasia after refractive surgery
• Axial topography consistent with corneal ectasia
For keratoconus patients only:
• Topographic evidence of keratoconus with a diagnosis of mild, moderate or severe keratoconus
• Maximum corneal curvature as measured by steepest keratometry (Kmax) value ≥ 47.00 D
Contact lens wearers only: manifest refraction must be stable between two visits which occur at least 7 days apart
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
Exclusion Criteria
Eyes classified as either normal, atypical normal (except corneal ectasia), or keratoconus suspect on the severity grading scheme
A history of previous corneal surgery (other than LASIK or PRK for subjects with corneal ectasia) or the insertion of Intacs in the eye(s) to be treated
Corneal pachymetry that is < 375 microns prior to epithelial debridement at the thinnest point in the eye to be treated
Eyes which are aphakic or pseudophakic and do not have a UV blocking lens implanted
A history of delayed epithelial healing in the eye(s) to be treated
Patients with nystagmus or any other condition that would have prevented a steady gaze during the CXL treatment or other diagnostic tests
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
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Treatment Groups
15mW/cm2
for 8 minutes
Epithelial removal
0.12% riboflavin1 gtt/2 mins for 20 mins
Irradiated at 15 mW/cm2
for 8 minutes (7.2 J/cm2)
30mW/cm2
for 4 minutes
Epithelial removal
0.12% riboflavin 1 gtt/2 mins for 20 mins
Irradiated at 30 mW/cm2
for 4 minutes (7.2 J/cm2)
45mW/cm2
for 2 minutes and 40 seconds
Epithelial removal
0.12% riboflavin 1 gtt/2 mins for 20 mins
Irradiated at 45 mW/cm2
for 2 min 40 sec (7.2 J/cm2
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
Goals and Key Benefits
• Provide patients access to treatment for current unmet medical need in an orphan population
• Greatly increase patient comfort during treatment due to shorter UVA irradiation time
• Allow qualified contralateral eyes to be treated
• Gain deeper understanding of safety and efficacy of higher powers of UVA irradiation for corneal collagen cross-linking
The VibeX™ / KXL™ System is not approved for sale in the United States MA-000178 Rev. C© 2012 Avedro
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FDA STUDY
• 2 year follow‐up
General success
Great Success!!! Consensus of literature
• CXL prevents further vision loss in over 95% of patients
• 60‐70% of patients having improved vision
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Complications
13 y/o white male – 5 days p/0 – lost bcl 2 days ago
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Father brought son in because eye seemed red
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Child reports no pain – F/U BCL for 2 days
No improvement with BCL for 2 days, 1 days post pressure patch
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29 year old black male
• Very poor bcva
• OS worse than OD
Initial presentation
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Do We Dare?
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2 months post cxl
2 months post cxl
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3.5 Diopters of flattening
2.5 Diopters of corneal flattening
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15 year old Hispanic Male
1 day post op
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1 week p/o
Studies
• Being investigated for a treatment of infectious keratitis
• Effective treatment depth of 300 microns may limit effectiveness
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Studies
• Treating corneal edema
• How long will the effect last
Studies
• Combining CXL with thermal or microwave procedures that transiently modify corneal shape
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Studies
• CXL for post‐RK ectasia and vision fluctuations
ARVO 2013
• Topographically Guided Corneal Cross‐Linking • David B. Usher
– Uses eye tracker and mirror system to control corneal illumination
• Patterned collagen crosslinking had an effect on corneal astigmatism.
• Finite Element Analysis of Treatment of Corneal Astigmatism with Collagen Crosslinking IBRAHIM SEVEN1
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PIXEL
• Photorefrative Intrasromal Crosslinking
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Enhanced Crosslinking
• Breathing new life into CXL
• Pulse light therapy
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Is this a surgery?
