Testing:UCVABiomicroscopy

( d )MRx (3 d )Penta/Topo (3 d )BCVA (1 mo )BCVA (1 mo )IOP (1 mo )

*differs per study

InfectionE i ff l dEpi-off only reported

Corneal Haze and ScarringEpi-off only reportedp o o y epo ted

Progression of diseaseIntraocular Inflammation

f fWorsening of refractionInability to tolerate contact lensesNeed for PKPNeed for PKP

SpectaclesBe careful with refraction!

Often different axis vs. preop RxHave patient rotate dial of axis in phoropterHave patient rotate dial of axis in phoropter

Contact LensesMost patients

Wait 2 wks-4 mos po prior to fitting (study and d d )surgeon dependent)

Combination procedures (CK-CXL, Intacs-CXL) less stable initially

Healthy anterior segment (many have been wearing CL p CXL)P ti t Ed fit b i dPatient Ed: refits may be requiredAlways begin with a new refraction, topo, and Ks

Fitting should be no different than non-CXL patients—Fitting should be no different than non CXL patientsunless cornea and/or refraction change in the future

Soft S hSphereToricKC-specific designs (NovaKone, Alden, Kerasoft p g ( , ,IC, B+L)

HybridClearKone or UltraHealth (SynergEyes Inc )ClearKone or UltraHealth (SynergEyes, Inc.)

GP Small diameter for KCLarge corneal for KC, post-RS, PKPScleral

Central: 100-400 l (um clearance (use

optic section)MidperipheryMidperiphery-Limbus: clearance (use Co blue light)(use Co blue light)Periphery:alignment; no lift-off or vessel blanching

Terry Lim, MDChairman, Cornea External Disease

Duke UniversityDuke UniversityDepartment of Ophthalmology

Shared guidelines that are based on more than 20 li i l i l20 clinical trialsEvidence of progression over 12 to 24 monthsWill have an increase of more than 1 D in termsWill have an increase of more than 1 D in terms of the steepest keratometry readingsAn increase of at least 1 D in regular astigmatism g gand a myopic shift of at least 0.5 DAn increase of at least 1 D in regular astigmatism and a myopic shift of at least 0 5 Dand a myopic shift of at least 0.5 D

Will have the presence of central or inferior steepening, axial topography consistent with keratoconus/ectasiaSteepest manual K of at least 47Steepest manual K of at least 47Pachymetry of at least 300 microns to 400 microns at the thinnest pointmicrons at the thinnest point

Hashemi H Seyedian MA Miraftab M et al Corneal collagen cross-linking with riboflavinHashemi H, Seyedian MA, Miraftab M et al. Corneal collagen cross linking with riboflavinand ultraviolet a irradiation for keratoconus: long-term results. Ophthalmol 2013Aug;120(8):1515-20.

DESIGN T l t th l t lt f l ll li ki (CXL) iDESIGN: To evaluate the long-term results of corneal collagen cross-linking (CXL) inpatients with progressive keratoconus (40 eyes, 32 KC) patients .MAIN OUTCOME MEASURES:BCVA, UCVA, MRSE, max-K, mean-K, CCT, and anterior and posterior elevation at the , , , , , , papex-baseline; 1, 3, 6 months after CXL; 1, 2, 4, and 5 years later. RESULTS:The mean K max K UCVA and astigmatism showed no change over time during these 5The mean-K, max-K, UCVA, and astigmatism showed no change over time during these 5years. After the first year, BCVA, MRSE, and CCT showed no change and stabilized, whereas elevation readings continued to decrease up to 5 years after CXL.CONCLUSIONS:Treatment of progressive keratoconus with CXL can stop disease progression, without raising any concern for safety, and can eliminate the need for keratoplasty.

A Randomized, Controlled Trial of Corneal C ll C Li ki i iCollagen Cross-Linking in progressive Keratoconus 3 Year ResultsOphthalmology 2014 Witting-Silva et alOphthalmology 2014 Witting Silva, et al.36 month results of CXL using riboflavin 0.1% solution for 15 minutes with 30 min of UV-A (3 W/ 2)(3mW/cm2)F/U @ 3,6,9,12,24,36 month intervals100 eyes with progressive keratoconus were100 eyes with progressive keratoconus were randomized into CXL treatment or control groups

At 36 Months there was a sustained improvement in Kmax, UCVA, BCVA after CXL, whereas eyes in the control group demonstrated further progressiondemonstrated further progression.

O'Brart DPS, Kwong TQ, Patel P, et al.f ll f b fl l lLong-term follow-up of riboflavin/ultraviolet

A (370 nm) corneal collagen cross-linking to halt the progression of keratoconushalt the progression of keratoconusBr J Ophthalmol 2013;997:433-437Abstract

T d i l ffi fTo determine long-term efficacy of riboflavin/ultraviolet A corneal cross-linking (CXL)

Methods 30 patients/ eyes who had undergone epi-off CXL were examined 4-6 years later.CXL were examined 4 6 years later.

spherical equivalent error (SEQ) increased by +0.72 dioptres (D)

SEQ increased by +0.82D (p<0.001),

(p<0.002)corrected distance visual acuity (CDVA) improved (p<0.005)mean simulated keratometry (Sim

(p<0.001), CDVA improved (p<0.03), mean Sim K reduced by 0.84D (p<0.00001), CAP reduced by 1 16Dmean simulated keratometry (Sim

K) reduced by 0.27D (p<0.04)cone apex power (CAP) reduced by 0.4D (p<0.02)

d i i i d

CAP reduced by 1.16D (p<0.0005), and root mean square (RMS) (p<0.0001), coma (p<0.0001),

secondary astigmatism improved (p<0.03) compared with preoperative values.

p ,secondary astigmatism (p<0.005) and pentafoil (p<0.05) decreased

1 Year 4-6 Year6

• No treated eyes progressed. • None lost >1 line of CDVA. • Seven untreated fellow eyes progressed.

• CXL is safe and effective.

Desire to reach consensusKeratoconusEctatic diseases

Focus onFocus on DefinitionConceptsClinical ManangementSurgical Treatments

Resulted in the diagnosis and management of keratoconus and other ectatic diseases via worldwide insightConclusion resulted inConclusion resulted in

DefinitionsStatementsRecommendations

Ophthalmologists with experience in the management of keratoconus and ectaticdiseasesAuthorship of scientific publications in highAuthorship of scientific publications in high-impact medical journalsWide recognition by the specialized medicalWide recognition by the specialized medical communityWilling to comply with the initial question g p y qrounds, face-to-face meeting, and project timelines

Worldwide geographic distributionRepresent 4 Ophthalmological Cornea socities

A i C S i t (A i )Asia Cornea Society (Asia)Cornea Society (USA and international)EuCornea (Europe)( p )PanCornea (Latin America, USA and Cananda)

Each society had 4 experts plus coordinators

Abnormal POSTERIOR EctasiaAbnormal Corneal Thickness DistributionClinical Non-inflammatory corneal thinning

Values and reference points vary based on device used for screeningdevice used for screening

KeratoconusPellucid Marginal Degeneration (PMD)KeratoglobusPost Refractive Surgery Ectasia

Terrien Marginal DegenerationDellenInflammatory Melts

Keratoglobus and Keratoconus are different clinical entitiesTrue unilateral keratoconus DOES NOT EXISTThi i l i dThinning, location and pattern are aspects that distinguish Keratoconus, PMD and KeratoglobusKeratoglobus

Full corneal thickness mapSlit lamp examAnterior curvature mapAnterior tomographic elevation map

Central Pachymetry

This is because Keratoconus can be present in a cornea of normal thickness

Tomography (Scheimpflug or OCT)*

Posterior corneal elevation abnormalities must b di ild b li i lbe present to diagnose mild or sub-clinical

keratoconus

*Best and Most Widely Available testsBest and Most Widely Available tests

Consistent change in at least 2 of the 3 following parameters

Steepening of the anterior corneal surfaceSteepening of the posterior corneal surfaceSteepening of the posterior corneal surfaceThinning and/or an increase in the rate of corneal thickness change from the periphery to the thinnest

ipointChanges need to be consistent over time and above normal variabilityabove normal variability

A change in both UCVA and BSCVA is NOT required to document progressionTesting for progression should be SHORTER for younger patientsfor younger patientsThe same measurement platform should be used in sequential examinationsused in sequential examinations

Down SyndromeR l i f ff d i di id l / iRelatives of affected individuals/patients

Especially in youngOcular allergy and systemic atopygy y pyEthnic factors (Asian and Arabian)Mechanical factors

Eye rubbing and Floppy eyelid syndromeEye rubbing and Floppy eyelid syndromeConnective tissue disorders

Marfan syndromeEhl D l dEhlers-Danlos syndromeLebers congenital amaurosis

The following findings are mandatory to diagnose keratoconusAbnormal posterior elevationpAbnormal corneal thickness distributionClinical noninflammatory corneal thinning

Keratoconus and PMD are different clinical presentations of the same diseaseThe aspect that distinguishes keratoconus PMD and keratoglobus is “thinning locationThe aspect that distinguishes keratoconus, PMD, and keratoglobus is thinning location and pattern”Keratoconus and PMD are best differentiated by a combination of

Full tomographic corneal thickness mapSlit-lamp examinationSlit lamp examinationAnterior curvature mapAnterior tomographic elevation map

As opposed to “thinning disorders” the following are classified under “ectatic diseases”KeratoconusKeratoconusPMDKeratoglobusPostrefractive surgery progressive corneal ectasia

K t l b d k t diff t li i l titiKeratoglobus and keratoconus are different clinical entitiesTrue unilateral keratoconus does not existThe best current and widely available diagnostic test to diagnose early keratoconus is tomography (Scheimpflug or optical coherence tomography)

Currently, there is no clinically adequate classification system for keratoconuskeratoconusPosterior corneal elevation abnormalities must be present to diagnose early or subclinical keratoconusSecondary induced ectasia may be caused by a pure mechanical y y y pprocess (and can be unilateral)Central pachymetry is the least reliable indicator (determinant) for diagnosing keratoconusThe pathophysiology of keratoconus is likely to include the following components

Genetic disorderBi h i l di dBiochemical disorderBiomechanical disorderEnvironmental disorder

Placido based topography analyzes the central anterior cornealPlacido-based topography analyzes the central anterior corneal surface, whereas tomography (Scheimpflug and/or optical coherence tomography) analyzes the anterior and posterior cornea and produces a near full corneal thickness map

Ectasia progression is defined by a consistent change in at least 2 of the following parameters where the magnitude of the change is above the g p g gnormal noise of the testing system

Progressive steepening of the anterior corneal surface Progressive steepening of the posterior corneal surfaceProgressive thinning and/or an increase in the rate of corneal thicknessProgressive thinning and/or an increase in the rate of corneal thickness change from the periphery to the thinnest point

The changes need to be consistent over time and above the normal | variability (ie, noise) of the measurement system (this will vary by system). Al h h i i f i d b d i BSCVAAlthough progression is often accompanied by a decrease in BSCVA, a change in both uncorrected visual acuity and BSCVA is not required to document progressionRisk factors for keratoconus:

Down syndrome, relatives of affected patients especially if they are young, Ocular allergy and systemic atopyEthnic factors (Asian and Arabian), Mechanical factors eg eye rubbing floppy eyelid syndromeMechanical factors, eg, eye rubbing, floppy eyelid syndrome,Connective tissue disorders (Marfan syndrome), Ehlers–Danlos syndrome and Leber congenital amaurosis

Halting disease progressionVisual rehabilitation

Verbal Guidance to the patient to not rub one’s eyesUse of topical antiallergenic medication in patients with allergypatients with allergyUse of topical antiallergenic medications in patients with atopy or history of eye rubbingpatients with atopy or history of eye rubbingUse of topical lubricants

There is no direct relationship between dry eye and keratoconusUse of eye drops without preservatives is preferable in keratoconic patientspreferable in keratoconic patients

PF agents reduce irritation and epithelial trauma

Subjective refraction should be attempted in all patients with ectasiaAberrometry my help determine the refraction early in the disease processrefraction early in the disease processPAL’s are not contraindicated by rarely successfulsuccessful

Contact lenses do not halt or slow the progression of corneal ectasiasCosmetic contact lenses should be discouraged due to difficulty in contact lensdiscouraged due to difficulty in contact lens fitting and THE INCREASED RISK OF COMPLICATIONS FROM A POORLY FITCOMPLICATIONS FROM A POORLY FIT CONTACT LENS

Should be used in cases of unsatisfactory vision with glasses or SCL’sGas-permeable are preferred and should be tried initially in patients with keratoconustried initially in patients with keratoconusIf failed in RGP’s then attempt

HybridHybridToric or BitoricSpecialty Keratoconic soft or rigid lensPiggy-backScleral lenses

Careful evaluation in cases of Down syndromePregnancy can contribute to the acceleration of ectasia progressionof ectasia progressionIn cases of acute hydrops non surgical or less invasive surgical management such asinvasive surgical management such as intracameral gas should be attempted before pregnancy

The 2 most important goals of management are halting disease progression and visual rehabilitation. Verbal guidance should be given to patients regarding the importance of not rubbing one’s eyes, use of topical antiallergic medication in patients with allergy, and use of topical lubricants (in the case of ocular irritation) to decrease the impulse to eye rubIn cases of allergy or if there is any allergic component, patients should be treated with topical antiallergic medication and lubricants. Topical multiple-action antiallergic medications (ie, antihistamines, mast cell stabilizer, antiinflammatory) should be used in patients with keratoconus with atopy or history of eye rubbingThere is no direct relationship between keratoconus and dry eyep y yPreservative-free agents are preferred as they are associated with less irritation and epithelial trauma compared with agents with preservativesSubjective refraction should be attempted in all patients with corneal ectasia. Aberrometry may help to determine the optical correction in early diseaseProgressive type glasses are not contraindicated in eyes with keratoconus or otherProgressive-type glasses are not contraindicated in eyes with keratoconus or other ectasias, but they are rarely successfulContact and scleral lenses are extremely important for visual rehabilitationin patients with keratoconus and other corneal ectasias

Contact lens use does not slow or halt progression of corneal ectasiasRigid contact lenses should be used in cases of unsatisfactory vision with glasses or conventional soft contact lenses. Among the rigid contact lenses, gas-permeable lenses are preferred and should be tried initially , g p p yin patients with keratoconus. In a patient with keratoconus who has failed conventional corneal gas-permeable lenses, alternative contact lens options would be: hybrid lens (rigid center, soft skirt); toric, bitoric, and keratoconus design soft contact lens; keratoconus design corneal rigid gas-permeable contact lens; piggy-back; corneoscleralrigid gas permeable contact lens; piggy back; corneoscleral, miniscleral, and semiscleral contact lens; and scleral lensA careful evaluation for keratoconus is strongly recommended in patients with Down syndrome and should be considered in patients with known risk factors for developing keratoconus (Table 2)Pregnancy could contribute to acceleration of the progression of ectasiaIn acute hydrops, nonsurgical management should be attempted before keratoplasty

Surgery should be considered when patients were not fully satisfied with non surgical treatments

“Satisfied best corrected”Satisfied best-corrected

Available and performed by 83.3% of panelists

Other 16.7% would use it if availableVariety of techniquesVariety of techniquesCollagen Cross Linking is not a correct termCorneal Cross Linking is a correct termCorneal Cross Linking is a correct term

Extremely important for keratoconus with progressionVery important for post-refractive keratoectasia (does not say progressive)keratoectasia (does not say progressive)Important for treatment of keratoconus with a perceived risk of progression (not confirmed)perceived risk of progression (not confirmed)No consensus for sub-clinical keratoconus

Consensus on No age restrictionsShould be used in eyes with demonstrated progression

No consensus on age limit for treatment inNo consensus on age limit for treatment in keratoconic eye without evidence of progressionRarely indicated in patients over 40No consensus best UCVA that limits CXL treatment

i.e. Treat if better than 20/30?

Anterior lamellar keratoplasty (ALK)Deep anterior lamellar keratoplasty (DALK)Penetrating keratoplasty (PK)Intra corneal ring segments (ICRS)

Photo therapeutic keratoplasty (PTK)Photo refractive keratoplasty (PRK)Conductive keratoplasty (CK)Incisional keratoplasty (IK)Microwave corneal remodeling

Clear lens extraction with IOL (sperical or toric) were uncommonly used by the paneltoric) were uncommonly used by the panel

DALKMost important patient-related factor is CL intolerance

PKPKMost important factor is corneal scarringPost hydrop scarringCL intoleranceLow corneal pachymetry (below 200microns)

High risk for hydropsHigh risk for hydropsPrevious failed corneal surgery

Any form offered to 21%-60% eligible keratoconic patientsIn patients with no prior hydrops

Eith ALK DALK f d i th 60% fEither ALK or DALK performed in more than 60% of patients

In patients with prior hydropsp p y pALK or DALK performed in 0% to 20% of patients

No prior hydropsOver 51% would perform DALK big bubble

Microkeratome ALK is never performedOth ALK i f d l th 25%Other ALK is performed less than 25%

Manual layer by layer predescemetic DALK (pdDALK) with viscodissectionpdDALK with Melles techniqueFemtosecond laser assissted DALK

Over half the panel have performed femtosecond laser-assisted PK for keratoconus

Of those who perform femto PK only perform it onOf those who perform femto PK, only perform it on 1%-20% of their cases

Majority of panelists currently perform a non laser technique

dDLAKPKICRS

dDALKdDALKPK

Young (eg, 15-year-old) patient with stable KCN with satisfactory vision with glassesg

Prescribe glasses only or in combination with contact lenses or CXLYoung (eg, 15-year-old) patient with progressive KCN with satisfactory vision with glasses

Perform CXL and prescribe glasses 6 contact lensesPerform CXL and prescribe glasses 6 contact lensesOlder (eg, 55-year-old) patient with stable KCN with satisfactory vision with glasses

Prescribe glasses only or with contact lensesOlder (eg, 55-year-old) patient with progressive KCN with satisfactory vision with glasses?

Perform corneal cross-linking only or with prescription of glasses/ contact lenseslenses

Patient with stable KCN with unsatisfactory vision with glasses but satisfactory vision with rigid contact lenses and tolerates them well? This patient has a spherical equivalent of moderate myopia [eg, 5 diopters (D)]

P ib t t l (i l di l l l )Prescribe contact lenses (including scleral lenses)Patient with stable KCN with unsatisfactory vision with glasses but good vision with rigid contact lenses, and tolerates them well? This patient has a spherical equivalent of high myopia (eg, 15 D)

Patient with stable KCN with unsatisfactory vision with glasses and contactand scleral lenses, or who does not tolerate contact or scleral lenses?,This patient has a spherical equivalent of moderate myopia (eg, 25 D)

Perform dDALK. Consider ICRS in eyes with adequate corneal thickness and minimal to no scarring

Patient with stable KCN with unsatisfactory vision with glasses and contactPatient with stable KCN with unsatisfactory vision with glasses and contact and scleral lenses, or who does not tolerate contact or scleral lenses? This patient has a spherical equivalent of high myopia (eg, 15 D)

Perform dDALKfPatient with stable severe KCN with unsatisfactory vision with glasses and

contact and scleral lenses? This patient has moderate anterior corneal scarring but no evidence of previous corneal hydrops

Perform dDALKPatient with stable severe KCN with unsatisfactory vision with glasses and contact and scleral lenses? This patient has moderate anterior and deep corneal scarring with evidence ofof previous corneal hydrops

PK alone or attempt pdDALKPK alone or attempt pdDALK

Requires 2 of the following:Steepening of the anterior surfaceSteepening of the posterior surfaceThinning or changes in the pachymetric rate ofThinning or changes in the pachymetric rate of change

Magnitude of changes is unknownYOUNGER PATIENTS SHOULD BE EXAMINED FOR CHANGE AT SHORTER INTERVALS AS ECTATIC

CHANGE CAN PROGRESS RAPIDLY IN THISCHANGE CAN PROGRESS RAPIDLY IN THIS GROUP

Anterior and posterior viewsSignificant importance of the posterior cornea as an early indicator of ectatic changeP i l f d l i i hPosterior corneal surface and alteration in the corneal thickness progression are necessary to diagnose keratoconusto diagnose keratoconus

Items needed to differentiate:Anterior and posterior tomographyCorneal thickness mapSlit lamp examSlit lamp examAnterior surface measurements

Different clinical presentations of the same basic disease processEctatic diseases:

K tKeratoconusPMDPost refractive surgery ectasiag yKeratoglobus

MultifactorialGeneticBiochemicalBiomechanicalEnvironmental

All assuming good candidatesAnyone with progressive ectasia should undergo CXL no matter what age level or visionvisionOK to proceed with CXL even if patients were happy with their visionhappy with their vision

What is the new estimate or incidence of Keratoconus?Keratoconus?Why weren’t Yaron Rabinowitz, MD Stephen Klyce, MD and Steven Wilson, MD included in the panel?panel?Why is there no information on contact lens fitting, materials, design and follow-up?Why no Optometrists if they deal with aWhy no Optometrists if they deal with a significant part of the non surgical and post operative patient?How is there is no direct relationship between dryHow is there is no direct relationship between dry eye and keratoconus?Contact lenses are just wrong…

Why no information on placido disc technology?Why no discussion about biomechanical properties of the cornea?properties of the cornea?Why no information or recommendation of epi-on or epi-offepi on or epi offIf keratoconus is bilateral, should you treat a 20/20 eye non-keratoconic eye to prevent / y y pthe progression?Is prophylactic treatment recommended?