U

pdate on Keratoconus Diagnosis and

Treatment

Mahdavi MD

SCLAFANI

“Keratoconus is a clinical term to describe a condition in which the cornea assumes a conical shape because of thinning and protrusion” SCLAFANI

Keratoconus History

Blurred vision Distortion Photophobia Monocular polyopia Halos Patient presents with frequent eyeglass changes SCLAFANI

KCN HISTORY

Non-inflammatory 1/2000-5000 Central 2/3 AR/AD Inheritance Females =Males Presents initially at puberty & progression varies, stability in 30s SCLAFANI

“Why don’t we see elderly patients with keratoconus”

Do they die younger NO Do they not visit POSSIBLE Have they CE/PKP POSSIBLE THEORY BY KRACHMER  The eye becomes more rigid as the patient ages and therefore the condition stabilizes SCLAFANI

ASSOCIATED SYSTEMIC CONDITIONS

Vernal KC Atopic Dermatitis Down’s Syndrome Floppy Eyelid Syndrome Mitral Valve Prolapse Ehlers-Danlos Syndrome Osteogenesis Imperfecta Lawrence-Moon-Biedl Syndrome Neurofibromatosis Psuedoxanthoma Elasticum SCLAFANI

ETIOLOGY OF KCN

History of trauma that causes weakness Recurrent trauma due to rubbing from  Blepharitis, CL/lids, 53% have atopic dx Inflammatory component !!!

  Decrease proteinase inhibitors Increase collagenase   Premature keratocytic apoptosis Increase cytokine binding SCLAFANI

Basic Science Research

KCN have higher # of mitochondrial DNA deletions that leads to decrease oxidative phosphorylation… increase H 2 0 2 Causes leakage, damages proteins, and results in oxidative stress Leads to apoptosis, abnormal healing, inflammation.

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Basic Science Research

Yaron Rabinowitz, MD UCLA KCN have suppressed Aquaporin 5 (AQP5) AQP5 is the water transport gene that is responsible for cell migration and wound healing.

Quantitative PCR testing (epithelial cells) could diagnose this SCLAFANI

RESEARCH MAY INDICATE NEW THERAPIES

KCN is unlikely a single gene defect  Chromosome 5, 21 Multiple genes in a common pathway Those with the defect may develop KCN naturally or only if exposed to factors that induce oxidative stress: CL over-wear, UV, allergy or refractive surgery TX: Anti-inflammatory, Anti-oxidant SCLAFANI

RETINOSCOPY

Scissors Reflex Against motion that breaks apart Represents multiple refractive powers within the optic zone SCLAFANI

KERATOCONUS-SLIT LAMP FINDINGS FLEISCHER RING abrupt change in curvature 50% VOGT’S STRIAE 1 st Sign 65% STROMAL THINNING STROMAL SCARS ENLARGED CORNEAL NERVES ACUTE HYDROPS 5% SCLAFANI

FLEISCHER RING

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VOGT’S STRIAE

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STROMAL SCARS

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ACUTE HYDROPS

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EXTERNAL FINDINGS

MUNSONS SIGN SCLAFANI RIZZUTIS SIGN

Keratoconus- Keratometry

Steepening begins infero-temporally and progresses clockwise TOPOGRAPHY- more sensitive PLACIDO RINGS- get closer SCLAFANI

PLACIDO RING IMAGES

Rings that are closer together represent areas of steeper curvature May indicate a tight suture applicable SCLAFANI

ELEVATION (FLOAT) MAPS

Predicts the relative elevation or depression of the cornea (in mm) using a computer generated BEST FIT SPHERE as a reference and fit at the steepest point SCLAFANI

ELEVATION MAPS PREDICT Na-FL PATTERN

+ VALUES- warm colors points higher than sphere = elevation Areas of bearing or touch - VALUES- cool colors points lower than sphere = depression Areas of pooling SCLAFANI

PELLUCID MARGINAL

Tear meniscus can creates pseudo-PMD SCLAFANI

PMD vs. KCN

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PSEUDOKERATOCONUS

Corneal warpage topography can mimic KC Repeat topography must be performed and a measurable change would indicate pseudo KC Evaluation of elevation maps at steep zone: Predicts the elevation or depression of the cornea if the best fit sphere was on cornea SCLAFANI

POSTERIOR KERATOCONUS

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KCN Effects on Vision

Tim McMahon, OD 60% reduction in VA is due to curvature, not just high cylinder RGP corrects cylinder however HOA remain COMA May consider reverse geometry CLS Reduced low contrast VA Reads chart slower SCLAFANI

COMA Z

3 1 Similar to SA except that it concerns off axis peripheral rays that cause a comet-shaped image deformity to non-axial portions of the image.

Minimal Post refractive surgery “Potato chip” due to flap hinge and shows the most dynamic change.

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SCLAFANI Refractive Surgery  Corneal laser refractive surgery: pre-op, enhancement options   Phakic IOLs Corneal refractive implants: Intacs Anterior Segment Imaging and Surgery  Corneal Imaging and Measurement   Iris Imaging and Evaluation Trauma Assessment

Visante Applications Anterior Segment Imaging and Surgery

Corneal Imaging and Measurement imaging and evaluation of corneal pathologies penetrating keratoplasty lamellar keratoplasty endothelial keratoplasty keratoconus imaging and assessment anterior segment imaging through opaque corneas SCLAFANI

Terrien‘s Marginal Degeneration

SCLAFANI image courtesy of Dr. M. Packer

Evolution of KCN: Ectasia to Hydrops

SCLAFANI image courtesy of Prof. G. Baikoff

KCN/Open Angle (ML)

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KCN- Thinning (ML)

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Indications for Intra-Limbal Lenses

KCN RGP dropouts Pellucid Marginal Post-PKP Astigmatic corneas SCL failures: due to neovascularization or poor visual acuity.

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Large Diameter Lenses

Corneo- Scleral 12.9 mm- 13.5 mm Semi- Scleral 13.6 mm- 14.9 mm Mini- Scleral 15.0 mm-18.0 mm Scleral Bearing, minimum corneal clearance Full Scleral 18.1 mm- > 24+ mm Scleral Bearing, maximum corneal clearance SCLAFANI Dyna Intralimbal (Lens Dynamics) Macrolens (C&H) Jupiter (Innovations in Sight) GBL (Con-Cise) Robert Breece, OD

Intra-Limbal Fitting

BC is Flatter than expected   K @ 4-5mm temporal vs. Average Mid K +.2mm

Goal       Light feather touch .2mm < corneal diameter (11.3 OAD) .1-.2 mm movement .2mm edge clearance Menicon Z or Extreme Unique ph or Claris SCLAFANI

SOFT LENS OPTIONS FOR KERATOCONUS

Soft Spheres Soft Torics X-cel Flexlens Tricurve    Basecurve 6.0 - 9.9

Diameter 10.0-15.0

Center Thickness .45

dK 13.2

Continental, Gelflex USA, Ocu-Ease (Ocuflex K) SCLAFANI

SUPER NOVA HydroKone

™

Innovations in Sight

Benz 5x material,Glycerol Methacrylate

POSTERIOR

:  Less dehydration, flexure,better optics Steep central curve, flatter paracentral peripheral curve all aspheric Fit the normal peripheral cornea & sclera like standard SCL. The central posterior curve provides sagittal depth to touch

ANTERIOR

: Central optical surface that quickly tapers to maximize 02 Low riding More movement SCLAFANI

Innovations in Sight

SUPER NOVA HydroKone

™ Base Curves: 4.1 to 9.3 Diameters: 12.0 to 17.0

Paracentral: 8.0-9.2

Sphere: +50.00 to -75.00

Cylinder: -0.25 to -50.00

Axis: 1 to 180 in 1 degree steps Mean K + 1mm Do not use H2O2 due to thickness EXPECT MORE MOVEMENT (5.3-8.5) (14.8) (8.6) SCLAFANI

SynergEyes™

A

High Dk Hybrid

Material   Paragon HDS 100 GP Center 27% Water Non Ionic Skirt (Group I) Paragon HDS 100® Rigid Center Non-Ionic 27% water Hydrogel Skirt Design        14.5 mm over all diameter 8.4 mm rigid center 7.8 mm optic zone 2-4skirt radii choices for each base curve radius Skirt thickness consistent across full power range Engineered edge HyperBond™ junction technology 8.4 mm 14.5mm

SynergEyes KC

Prolate ellipsoid base curve Spherical Skirt begins at 9.0 mm diameter 3 skirt curve options for fitting flexibility FDA Clearance December 2005 SCLAFANI

Aspheric Base Curve

5.7mm (59.00) 5.9mm (57.00) 6.1mm (55.50) 6.3mm (53.50) 6.5mm (52.00) 6.7mm (50.50) 6.9mm (49.00) 7.1mm (47.50)

SynergEyes KC Diagnostic Set Parameters Power -14.00

-14.00

-12.00

-10.00

-8.00

-6.00

-5.00

-4.00

Flat Skirt

8.5

8.5

8.5

8.8

8.8

8.8

8.8

9.1

Medium Skirt

8.2

8.2

8.2

8.5

8.5

8.5

8.5

8.8

Steep Skirt

7.9

7.9

7.9

8.2

8.2

8.2

8.2

8.5

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SynergEyes Fitting

Lens Movement      .2mm to .3mm movement with blink Slight lag in upward gaze Free of scleral impingement Free to move on “push up” Free of “edge fluting” SCLAFANI

The Fitting Tips

• • Never prescribe Flatter than Flat K Counter-intuitive: Corneas

flatter

than 44.25D and

larger

than 12.0 mm: Steeper Skirt Corneas

Steeper

44.25D and

smaller

than 11.5 mm:

Flatter skirt

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Identical Apical Radius with Different HVID = different sagittal depth

3.60

2.96

12.0 mm 11.0 mm

UPDATES FOR SYNERGEYES

Proprietary materials that has a SiHy skirt and higher Dk GP The GP will have less flexure, will likely discontinue the enhanced profile To reduce peripheral crimping, the skirt curves will be multicurve: bi or aspheric CLEAR KONE : Additional KC lens for more ectopic or decentered peaks with reverse geometry to eliminate steep BC SCLAFANI

Vault the cornea yet aligns closer to cornea allowing lower powers Reverse geometry at skirt to allow more tear flow, easier removal SCLAFANI

TIPS ON PIGGYBACKS

SCL protects from RGP or environment Reduces epithelial damage due to touch Protects from apical nodules Concurrent EBMD High DK, easily replaced= SiHi Soft Modulus molds to highly toric/steep K +SCL to flatten the RGP - SCL to steepen the RGP fit SCLAFANI

Intra-Stromal Rings

Ring segments are placed into peripheral corneal channels outside the visual axis to correct low to moderate myopia by flattening the cornea without cutting or removing tissue form the central optical zone FDA approval of Intacs in 1999 for low/mod myopia. Recently approved for keratoconus in US July 2004 Principle benefit: delay or eliminate corneal graft Reversible/Removable SCLAFANI

Intacs Studies

By Wachler and et al.

 74 keratoconus eyes has insertion of intacs with F/U of 9 months 45% gain ≥ 2 lines BCVA (worst pre-opt) 51% had no effective changes 4% loss ≥ 2 lines of BCVA SCLAFANI

Single intrastromal corneal implant favored for paracentral cones Colin Chan, MD and Boxer Wachler,MD Compared 20 eyes (double) vs. 17 (single) Single used .25mm segment/ Double .25&.35

All had paracentral/peripheral cones Significantly better outcomes in change in cylinder, K values, UBVA, BCVA Single 2-3 line gain, Double 1 line gain SCLAFANI

Complications of Intacs for KCN

Undercorrection Overcorrection Neovascularization toward the Incision

Migration of One segment toward the Wound

Extrusion Stromal deposit Flap wrinkling (intracorneal inlays) Epithelial ingrowth Residual refractive error Complication rate ranges from 5-30% SCLAFANI

Biomechanical Effect of Combined Riboflavin-UVA

The cross-linking in KCN is abnormal Too elastic and the biomechanical resistance is 50% Loss of Bowman’s Kristen Fry, OD SCLAFANI

Biomechanical Effect of Combined Riboflavin-UVA

GOAL: Increase cross-linking Increase diameter  12% Anterior  5% Posterior SCLAFANI

C3-R Mechanism UVA 370nm Riboflavin .1%

Corneal Collagen Crosslinking

Stability

SCLAFANI Biomechanical Stiffness

Theo Seiler, MD

Initial work AJO, 2003 70% reduction in max K by 2D (N=23) Increase in rigidity by 329% Increase in spacing (1nm) between the collagen molecules leads to increase diameter with no effect on transparency (150nm) Increased resistance to enzymatic digestion Has been shown to be effective for iatrogenic ectasia in animals.

Bed < 400 um, severe endothelial damage SCLAFANI

PROCESS OF C3R-TX

Topical Anesthetic Epithelium is scraped  Acts as diffusion barrier, potential damage .1% Riboflavin drops q 5 min throughout  Protects the endothelium, lens, retina  Increases absorption into stroma 30 min. radiation 370 nm UVA –3mW/cm 3 Post-op FQ and pain relief Depth goes to 300 um therefore must have 400 um pachymetry to protect endothelium SCLAFANI

Studies by Eberhard Spoerl, PhD

Immediate Evidence of increased x linking: Resistance to swelling and stretching utilizing Reicherts air pulse deforms cornea and measures area of deformation. Increases anchoring and reduces bulge Cellular Process 24h-12 weeks Leads to apoptosis of keratocytes with late migration of keratoblasts that result in flattening 5 yrs, N = 60, BCVA >1.4 lines K flat 2.87 D SCLAFANI

Studies by Aldo Caporossi, MD University of Sienna, Italy

Suggests using it early in the disease to freeze tissue and prevent further ectasia Scrapes the epithelium prior to procedure.

12 eyes followed for 3months in 2004.

All showed improved UCVA, BCVA, and reduced steepness One side effect was transient stromal edema SCLAFANI

POTENTIAL USES OF C3R

Post-Lasik ectasia Prevent KCN regression/scars Post CK-to enforce result Post-CRT- to enforce result? epithelial Boxer Wachler, MD has shown this to be an effective treatment when combined with Intacts for KCN SCLAFANI

References

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2.

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4.

5.

6.

Colin J, Simonpoli-Velou S. The Management of Keratoconus with Intrastomal Corneal Rings. International Ophthalmology Clinics. 43(3):65-80, Summer 2003.

Kaiser P, Friedman N, et. al. The Massachusetts Eye and Ear Infirmary Illustrated Manual of Ophthalmology. Ed. 2. 2004.

Kunimoto D, Kanitkar K, et al. The Wills Eye Manual. Fourth Edition. Lippincott Williams & Wilkins 2004.

Roque M, Limbonsiong R, et. al. Myopia, Intracorneal Rings. August 14, 2002. www.emedicine.com/oph/topic665.htm

Wachler B, Chandra N, et. al. Intacs for Keratoconus. American Academy of Ophthalmology. 2003. 1031-1039.

Weissman B, Yeung K, et al. Keratoconus. Jan 29, 2005 www.emedicine.com/oph/topic104.htm

SCLAFANI

Thank you

SCLAFANI