Keratoconus. Progressive bilateral ectasia. Onset puberty. Prevalence 1: % progress to transplantation. Pathogenesis unclear

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2 Keratoconus Progressive bilateral ectasia Onset puberty Prevalence 1: % progress to transplantation Pathogenesis unclear Increased pepsin and catalase Decreased collagen crosslinking cf normal

3 Conventional Treatment Options for Keratoconus Spectacles RGP Contact Lens Intra Corneal Ring Segments Corneal transplantation in 20% PKP DALK Like Nero, we fiddle while Rome Burns

4 Riboflavin / UVA Crosslinking Corneal strength reduced by 36% in KC especially young keratoconics Corneal collagen cross linking increases with age and diabetes Same process in human lens produces nuclear sclerotic cataract Inducing cross linking in the cornea may stop progression of keratoconus

5 Riboflavin / UVA Crosslinking Riboflavin 0.1% photosensitiser applied to cornea for 30 mins. UVA (370 nm) exposure 3 mw / sq.cm for 30 mins. Cross linking in anterior 350um of cornea Increases corneal strength by 328%

6 Main indication: progression Defining progression remains a challenge Coefficient of variability large in keratoconus >1.5 D in keratoconus <0.5 D in normal corneas Orbscan and refraction on presentation Try to leave RGP C/L out for 2 weeks prior Repeat 6 monthly for 2 years then annually Can be difficult to assess if progression or not

7 INDICATION: Progression of Keratoconus Criteria used in Clinical Trials Kmax >1D increase Kmax Kmin >1D increase Pachymetry >2% decrease in CCT Corneal apex power >1D increase MRSE > 0.5D change

8 INDICATION: Criteria of Southern Cross Progression: K Max 1.00 D increase over 2 years max. MRSE or cyl 3 D change over 6 months. Pachymetry 5% decrease over 6 months. Inclusions: BCVA 6/12 or better Age 14 to 35 years

9 Classical Protocol: Wollensak Method Topical anaesthesia Epithelial debridement Riboflavin q2.5 mins for 30 minutes Pachymetry every 5 minutes If cornea <400 um -> hypotonic solutions UV exposure for 30 minutes Riboflavin and pachy continued during UV Post op: TSCL, Antibiotic, Corticosteroid

10 Results Wollensak: initial study 52% stabilised 45% improved 3% worsened Wollensak G, et al. Riboflavin/ultraviolet-a- induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol 2003; 135(5): Siena Study: Controlled trial All treated eyes halted progression Control non treated eyes progressed by 1.5D Caporossi A, et al. Long- term results of riboflavin ultraviolet a corneal collagen cross-linking for keratoconus in Italy: the Siena eye cross study. Am J Ophthalmol 2010; 149(4):

11 SDZ Crosslinker

12 Complications Mild stromal haze: common, resolve after 1 year Sterile corneal infiltrates: 7% : respond to steroids, need to exclude infection Reduced BCVA: 2% 2 or more lines Microbial keratitis: 0.1% Epithelial defect and TSCL Monitor closely post-op

13 Keratocyte and endothelial toxicity Keratocyte apoptosis down to 350Um depth after C3R Recovers over 1 to 2 years? UV damage to endothelium: Cytotoxic threshold for endothelium 0.35mW/cm.sq. Riboflavin shields deeper cornea >400um corneas, UV exposure < 0.18 mw /sq.cm. - no increased endothelial cell loss < 400 corneas -> increased endothelial toxicity and cell loss Important to not treat corneas thinner than 400um!!

14 Trans-epithelial Crosslinking Epithelium left intact Enhancers of epithelial permeability Benzalkonium chloride EDTA Topical anaesthetics Microabrasions Less pain Reduced risk of microbial keratitis

15 Trans-epithelial Crosslinking Demarcation line seems to be less deep 100um cf 300um? Shallower depth of effect Considered as first line treatment, with epithelium off crosslinking if it fails to halt progression Suggested use in children on first diagnosis before waiting for progression

16 Rapid Crosslinking Shorter UV exposure time, higher irradiation Same increase in corneal stiffness Same rate of prevention of progression Similar amount of post-op flattening AVEDRO: VibeX Rapid: riboflavin without Dextran UV 30mW for 3 minutes

17 Post LASIK Ectasia Rare, incidence 1 in 5000 LASIK Risk factors: Thin corneas Deep ablations Young age Pre-existing forme fruste keratoconus Management: RGP C/L ICRS PKP

18 Topography of post Lasik Thinning

19 Topography of Keratectasia

20 C3R for Ectasia: First described in 2005 Effective in halting progression Less dramatic response Lower incidence of reduction of maximum keratometry cf keratoconus Mainly strengthens the flap which does not contribute to corneal strength

21 C3R AND PRK in keratoconus Corneal collagen crosslinking To stabilise improvement in corneal shape To reduce chance of inducing further ectasia Topography guided PRK To reduce corneal irregularity Limited total depth ablation Limited attempt to correct refractive error Athens Protocol: Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M et al. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg 2009; 25(9): S807 S811.

22 C3R and PRK Timing of treatments? C3R then PRK Toughen cornea first then ablate it? More like a normal cornea to PRK Ablation removes crosslinked stroma May reduce effectiveness of crosslinking Simultaneous Only one painful treatment, one exposure to risk Flattening effect of C3R unpredictable: hypermetropia 400um residual bed required after PRK limits ablation Kanellopoulos AJ. Comparison of sequential vs same-day simultaneous collagen cross-linking and topography- guided PRK for treatment of keratoconus. J Refract Surg 2009; 25(9): S812 S818.

23 Other C3R uses: Peripheral Ulcerative Keratitis Increases corneal resistance to collagenase Reported use in corneal melts including PUK Microbial keratitis: Sterilising effect Reported use in cases not responding to antimicrobials

24 Summary Now a standard part of keratoconus management May prevent significant visual morbidity Safe and effective Increasing indications Evolving techniques to decrease pain, risks, surgical time May become a large demand on eye services