Keratoconus and collagen cross linking- Basic opthalmoscopy findings - presentation at www.eyenirvaan.com

1. KERATOCONUS AND
CORNEAL COLLAGEN
CROSS-LINKING
Isha Dave B.Sc (Hons), M.C Optom (UK)
Practicing Optometrist and Educator
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2. Keratoconus and Corneal
Collagen Cross-Linking

3. Keratoconus
 Cornea assumes a conical shape due to non-
inflammatory thinning of the stroma of the
central cornea
 Irregular astigmatism
 Reduced VA
 Normally affects both eyes (>90%), but
symptoms may present in one eye initially
 50% of fellow eyes will progress within 16 years
 Greatest risk within first six years of onset

4. Keratoconus
 Three types:
 Keratoconus associated with rare genetic
disorders
 Keratoconus in disorders where a common
association is reported

Down Syndrome

Leber’s Congenital Amaurosis

Marfan’s Syndrome
 Isolated Keratonconus with no associations

5. Epidemiology
 Table adapted from:
Gordon-Shaag et al, The Epidemiology and Etiology of Keratoconus. Int J Keratoco
Ectactic Corneal Dis. 2012; 1(1):7-15
Author Location Age
(yrs)
Sample
size
Prevalence
( /100,000)
Source
Hofstetter Indianapolis, USA 1-79 13395 500 Population
Tanabe Muroran, Japan 10-60 2601 9 Hospital
Kennedy Minnesota, USA 12-77 54 54.5 Hospital
Ihalainen Finland 15-70 294 30 Hospital
Santiago France 18-22 670 1190 Army Recruits
Pearson Midlands, UK 10-44 382 57 (Caucasion)
229 (Asian)
Hospital
Nielsen Denmark 772 86 Hospital
Jonas Maharashtra, India >29 4667 2300 Population
Millodot Jerusalem, Israel 18-54 981 2340 College Student
Population

6. Epidemiology
 Age
 Onset at puberty and progression
 CLEK study – Maximum prevalence in 2nd
, 3rd
and
4th
decade
 Gender
 Male > Female
 Georgiou et al: 2.6 x higher in males
 Ethnicity
 4.4 – 7.5 x greater prevalence in South Asian
community

7. Etiology – Genetic Factors
 Positive family history
 6%-13.5% based on patient’s verbal
responses (CLEK)
 Videokeratography investigation (Wang et
al):

3.34% in first-degree relatives
 No investigations carried out using corneal
topography

8. Etiology – Environmental
Factors
 Eye Rubbing:
 CHAR – Chronic Habit of Abnormal Rubbing
 Case-controlled studies – strong association
between CHAR and progression of KC
 Atopy
 Several studies show statistically significant
association
 Kaya et al: Atopic keratoconics had thinner and
steeper ectatic zones than non-atopic
keratoconics
 Contraversial
 Could be due to atopy-induced eye rubbing

9. CLEK Study
 The Collaborative Longitudinal Evaluation of
Keratoconus Study
 Multi-center, natural history study
 Goal:
 “..to prospectively characterize changes in vision,
corneal curvature, corneal status (including
corneal scarring) and quality of life in patients with
keratoconus and to identify the factors associated
with these changes over time.”
 1209 eligible subjects over 16 clinics across
USA

10. CLEK Study
Inclusion criteria:
 Aged 12 years and older
 Irregular cornea:

Distortion of keratometric mires

Scissoring of retinoscopic reflex
 Demonstrate atleast one biomicroscopic sign

Vogt’s Striae

Fleischer’s ring of 2mm or more

Corneal scarring typical of keratoconus
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11. CLEK Study
 Procedure
 Corneal Curvature

Change in FDACL using CLEK trial set
 BCVA

High and low contrast Bailey-Lovie Charts
 Quality of life

National Eye Institute Visual Function
Questionnaire (NEI-VFQ)
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12. CLEK Study

13. CLEK Study
 Results
 7 year decrease in both high- and low- contrast
acuity
 Average 8-year increase in corneal curvature –
1.60D

3.00D in 24% of subjects
 Flat vs. steep fit inconclusive in relation to corneal
scarring

Natural history of disease?
 VA reduced in patients with corneal scarring

14. CLEK Study
 Results

15. CLEK Study
 Results
 Quality of life

VA worse that 20/40 (6/12) showed lower
scores

Curvature more than 52D showed lower scores

Contact lens wearers showed higher scores
than non-cl wearers, but lower ocular pain
scores
 VA and corneal curvature affect Px’s QOL

16. Symptoms
 Reduced VA
 Diplopia
 Shadows
 Haloes
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17. Signs
 Fluctuating Rx
 Especially myopic
sphere and
cylinder
 Scissors reflex on
retinoscopy
 Apical
decentration on
topography
 Apical steepening
(conical
protrusion)

18. Signs
 Vogt’s Straie
 Fleischer’s ring
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19. Signs
 Apical scarring
 Munsen’s sign
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20. Management
 Managing VA:
 Spectacles
 Contact Lenses – Soft/RGP/Hybrid
 Traditional surgical intervention:
 Penetrating Keratoplasty
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21. Management
 Newer treatments:
 Layer selective keratoplasty (DALK, ALK,
PLK)
 Femto-assisted keratoplasty
 Intacs
 Corneal collagen cross-linking (CXL)
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22. Role of Collagen
 Regular matrix of collagen fibres – stromal
lamellae
 Provide support
 Collagen molecules strengthened by inter-
molecular crosslinks
 Keratoconus:
 Abnormality in types and numbers of crosslinks
 Central cornea begins to bulge forward

23. Cross-linking
 Well established technique – used in
synthetic polymer chemistry
 Manufacture of plastics, dentistry,
orthopaedics
 Increases mechanical strength of
material
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24. Cross-linking the cornea
 Use in cornea first discovered in 1998
 Use for keratoconus treatment first
reported in 2003
 Successfully used for post-LASIK
ectasia and PMD
 Strengthens cornea
 Flattening and regularisation of cone
 Reduction of astigmatism and myopia

25. Cross-Linking for the cornea
 CXL involves the use of riboflavin
(vitamin B2) and UVA light irradiation
 Riboflavin acts as a photo sensitizer for
the induction of crosslinks between
collagen fibrils as well as shielding the
underlying tissue from the effects of UVA
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26. Crosslinking cont…
 Interaction of riboflavin
and UVA produces a
reactive oxygen species
which forms additional
covalent bonds between
collagen molecules and
produces a
biomechanical stiffening
of the cornea.
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27. Technique
 Instillation of topical
anaesthetic drops
 Central 7mm of corneal
epithelium removed.
 Exposed corneal surface is
treated with the application of
riboflavin (vitamin B2) 0.1%
solution for a total of 30
minutes, starting 5 minutes
before the start of irradiation
 UVA radiation of 370nm at a
distance of 1cm from the
cornea is applied for a period
of 30 minutes
 Antibiotic drops are instilled as
a prophylaxis following
treatment
 Bandage contact lens inserted
until the epithelium has healed

28. Results
 Maximum analysis so far is 6 years
 Improvement in UCVA 1-3.6 lines
 Improvement in BCVA 1-2 lines
 Reduction in myopia of 0.40 – 1.14D
 Reduction in astigmatism of 0.93D
 Flattening of average K reading of 1.42 –
2.00D
 Postoperative regression of keratoconus
noted in 70% of cases

29. Patient Suitability
AGE
 Studies 10 - 60 years.
 More effective on younger
patients with more
progression
CONTRAINDICATION
 Corneal opacities, ocular
pathologies, corneal scarring,
Vogt striae, dry eye, corneal
infections, previous surgery
PROGRESSION
 Studies to date have used
varying methods to establish
progression.
CORNEAL THICKNESS
 Corneas < 400µm - significant
endothelial cell density decrease
and a permanent stromal scar
 Thickness of thinner corneas
can be increased by application
of hypo-osmolar riboflavin
solution following epithelium
removal

30. Complications
FAILURE
 < 2% acute
exacerbation of
neurodermatitis causing
progression of
keratoconus
 7.6% had an increase in
maximum K reading of
more than 1.00D.
HAZE
 grade of 0.06 noted at 12
months
 Permanent corneal haze is
more likely in thinner and
steeper corneas
 Persistent haze reduced
BCVA by 2 lines in 2.9%.
 A scar developed in 2.9%
of eyes

31. Complications
PAIN
 Removal of the corneal
epithelium caused post-
operative pain for 24-72
hours
MICROBIAL INFECTION
 Only as anecdotal case
reports – 5 in total
 Risk exists due to epithelial
debridement and use of a
soft contact lens.
 Decrease in BCVA even
with appropriate treatment
 Sterile conditions and post-
op review important
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32. The Future
Trans-epithlial
 Without epithelial removal
 Less post-operative
discomfort, shorter recovery
time, lower risk of infection
 Preoperative anaesthetic
eye drops containing
benzalkonium chloride
loosen the tight junctions of
corneal epithelial cells
 Animal studies have shown
only one fifth of the increase
in strength of cornea
compared with standard CXL
Flash-Linking
 Uses a customised
photoactive crosslinking
agent requiring only 30
seconds of UVA
exposure.
 Animal studies have so
far shown a similar
efficacy as standard
CXL
 Only through
measurement with
surface wave
elastometry

33. Acknowledgements
 Mrs. Preeti Singla
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