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Corneal collagen cross linking
This document discusses corneal collagen cross linking (C3R), a treatment for keratoconus. It begins by describing keratoconus and its symptoms. It then discusses the original C3R protocol developed by Seiler and Spoerl, which involves removing the corneal epithelium, soaking the cornea in riboflavin, and exposing it to UV light. Modifications to the protocol aim to reduce complications by using higher irradiance for less time, different riboflavin delivery methods, and leaving the epithelium intact. Studies show C3R increases corneal collagen bonds and rigidity while halting keratoconus progression in most cases. Contraindications and post-op care are also outlined
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Corneal collagen cross linking
- 1. CORNEAL COLLAGEN CROSS LINKING DrPAAVAN KALRA Department of Ophthalmology S P Medical College Bikaner
- 2. KERATOCONUS • Progressive, noninflammatory, ectatic disease of cornea • 1 in 2000 to 1 in 500 • Most common indication for PKP in west • Cornea becomes conical in shape with off centre apex • Myopic and irregular astigmatism • Begins at puberty, progresses eventually stops by 40 • Worsening of ectasia during pregnancy
- 3. • Increase inproteolytic enzymes • Decrease in enzyme inhibitors • Decreased total proteins, sulphated proteoglycans • Decreased inter fibrillar bonds in collagen • Uneven distribution of stromal lamellae. • Central/ paracentral thinning of stroma. • Slippage of lamellae and bowman’s layer • Biomechanical strength in about half the normal
- 4. • Glasses • Contactlenses – soft -spherical RGP -specialty RGP - rose k -scleral fitted • INTACS • Lamellar keratoplasty – DALK • PKP
- 5. LASER(ABLATIVE) REFRACTIVE SURGERY •keratoconus – contraindication – especially early, subclinical forms which tend to get missed • Post refractive keratectasia – LASIK / PRK – One of the most dreaded complication for refractive surgeon – 0.12 to 0.66 % – Central steeping due to weakened biomechanics of cornea – Myopic shift , astigmatic changes – May require Penetrating Keratoplasty
- 6. • Risk factors –Pre op pachymetry <500 microns – High myopia – Thick flap – flap later on doesn’t contribute to biomechanical stability – Low residual stromal thickness <250/300 microns – Pre op topographic abnormalities – FFKC and PMD Posterior float elevations > 40 mm Asymmetric inferior corneal steeping Skewed steep radial axes above and below horizontal meridian Bow tie pattern
- 7. CROSS LINKING • Increasein inter molecular bonds Natural in corneal tissue ageing diabetes – advanced glycation end products No keratoconus in type 1 DM Artificial Chemical gluteraldehyde – prosthetic valves Physical UV in dentistry Photo chemical C3R
- 8. • THEO SEILER •E SPOERL • G WOLLENSAK • CAPOROSSI • PINELLI • LECCISOTTI • CHAN • BRIAN BOXER WACHLER • KANELLOPOULOS • GULANI Animal studies and experiments – 1993 – 1997 1st report on clinical trial - 2003
- 9. • RIBOFLAVIN –vitaminB2 – intermediary metabolism Photo sensitizer and UV blocker Non toxic Absorption peak -> 365 – 370 mm • UV - A photo keratitis and skin cancer are caused by UV –B ( 290- 320mic) UV - A transmittance = 7 % across cornea saturated with riboflavin
- 10. • Release ofROS • Ionization of amino groups • Formation of new bonds • Type 2 photo chemical reaction
- 12. Effect on keratocytesand corneal nerves • Loss of subepithelial and anterior stromal nerve fibres. Loss of corneal sensations • Loss in number and rarefaction of keratocytes upto depth of 300 microns. • spongy honey comb like edema • Activated keratocytes appear after 3 months with decrease in edema • Densely populated activated keratocytes, disappearance of edema and reappearance of anterior stromal nerve fibres are seen by 6 months • Dense tissue around keratocytes upto 300 micron depth only – observed as subclinical haze and demarcation line on biomicroscopy
- 14. Effect on cornealstroma • Effect only in anterior 250-300 microns confirmed by histology, confocal microscopy and AS OCT • Increased intra and inter fibrillar bonds • Increased collagen fiber diameter by 12% • Increased resistance to collagenase digestion, mercaptoethanol and heat
- 15. • Biomechanical effect-Microcomputer based biomaterial testing machine - Increase in rigidity 328.9% and young modulus by factor of 4.5 • Thermo mechanical effect – heat dependent shrinkage – increase in temperature from 700 to 750
- 16.
- 17. Concern for endothelium,lens and retina
- 19. INDICATIONS • Documented Progressivekeratoconus on topography in young patient age < 30 years Mainly - halt and delay progression and hence need of PK May lead to reversal of ectasia • POST LASIK ECTASIA
- 20. CONTRAINDICATIONS • Corneal Scarring- central • Pachymetry < 400 microns at the thinnest point • Vogt striae • Dark micro striae in reticular pattern on confocal microscopy • Steep K > 58 D • Poor BCVA with hard contact lenses • High BCVA – 6/9
- 21. CONTRAINDICATIONS • Active oculardisease - allergy • Herpes keratitis • Severe dry eye • Children < 18 years • Pregnancy and lactation • Diabetes Mellitus
- 22. Pre op evaluation UCVA,BCVA & BSCVA REFRACTION – manifest spherical equivalent SLIT LAMP EXAMINATION KERATOMETRY TOPOGRAPHY – elevation based – orbscan II / pentacam PACHYMETRY (contact lens free period upto 2 weeks) AS - OCT and CONFOCAL MICROSCOPY give additional information
- 23. • COUNSELLING andCONSENT – procedure not for visual rehabilitation • Under sterile conditions in OT • Anti biotic eye drops • Topical anesthesia • Patching of the other eye • Preparation and draping • Insertion of eye speculum
- 24. ORIGINAL SEILER CROSSLINKING (DRESDENPROTOCOL) • Complete EPITHELIUM SCRAPING manually by blunt spatula– 7 mm zone • RIBOFLAVIN 0.1% in 20% dextran T500 in NS (pH=7, hyper osmolar) –1 drop every 3 mins for 30 mins
- 25. • Checking saturationof cornea with riboflavin : SLE with blue light – green fluorescence in AC • Checking calibration – irradiance • Intra op pachymetry (USG) > 400 microns • Patient instructed to look into centre of the light
- 26. • UV-A irradiationfrom 5 cm - @ 3mw/sq cm X 30 mins ( 5.4 J/ sq cm) • Proper focus and centration – loss of energy / hot spots • Riboflavin drops – every 5 mins • BSS to prevent desiccation during procedure • Solution protected from light
- 28. Protection of Sclera,goblet cells, limbus stem cells during procedure Cellulose sponge / merocel
- 29. RESULTS- DRESDON METHOD •(2003) 22 eyes steep K – flattening in 70 % patients by avg of 2D stable in 5 patients progressed in 1 by 0.28D progression in 23% of control by 1.5D improvement in refraction and BCVA by 1.26 lines • (2008) 111 eyes longer follow up steep K decreased by avg 2.29D, 3.27D, 4.34D in 1st, 2nd and 3rd year vision improved or remained stable in 96 % by 3rd year
- 30. POST OP • Healingof epithelial defect – 3-5 days Bandage contact lens / patching Cycloplegics, antibiotic , NSAID & artificial tears eye drops Oral analgesic SOS observed daily • Mild steroid eye drops for 3 – 6 weeks (FML 0.1%) • Review at 1 week, 4 weeks, 12 weeks, 24 weeks and 1 year • Topography, keratometry after 12 weeks • Patient can start using old RGP Lenses after 2 weeks • Temporary blurring of vision, FB sensation, pain • Prednsolone eye drops for persisting haze
- 31. COMPLICATIONS • Transient Cornealedema – lasts few days • CORNEAL HAZE • HOT SPOTS • CORNEAL SCARRING • ENDOTHELIAL BURNS • INFECTIONS • CORNEAL MELT • Persistence of epithelial defect • failure
- 32. MODIFICATIONS • More efficientdelivery of energy • Reduction of intra operative time • Reduction in patient discomfort • Reduction in chances of complications infection/slow healing/sub epithelial haze • Early rehabilitation • Bilateral treatment in one sitting
- 33. • EPITHELIUM REMOVAL Removalof epithelium by excimer laser PTK = 40 microns –> ‘no touch’ imp in post incision surgeries like RK Partial removal of epithelium Trans epithelial / EPI ON technique
- 34. • RIBOFLAVIN DELIVERY useof epi lasik well hypo osmolar solution for thinner corneas – 0.5% solution diluted in BSS 1:4, applied every 5 secs until intra op pachymetry reaches 400 microns Cornea should not be swollen > 80 microns
- 35. • IRRADIANCE -CBM Xlinker VEGA -higher irradiance and shorter duration – 7 mW/cm2 for 15 mins
- 36. CAPOROSSI CROSSLINKING TECHNIQUE (SIENNAEYE CROSS PROJECT) • Different illuminator - CBM(caporossi Baiocchi mazotta) X linker VEGA • 5 uv a LED array – sharper focus • Low power red laser sources - proper aiming 1 mm defocus / 0.2 mm defocus = 10% loss of energy • Micro camera and automated control
- 38. TRANSEPITHELIAL/ EPI ON(PINELLI) •Proparacaine – two drops every 5 mins for 15 mins • Application of riboflavin via merocel sponge for 5 mins – pre soak • Every 3 mins during procedure Penetration of riboflavin can be enhanced with EDTA and topical gentamicin 3 hr pre treatment – tensio actives
- 40. • Reported noendothelial toxicity • Controversy regarding riboflavin penetration and relatively higher delivery of energy to endothelium • Doubts about efficacy • Punctate epithelial defects may occur
- 41. KANELLOPOULOS INTRALASE CROSSLINKING In earlydisease, IntraLase femtosecond laser is used to create a corneal pocket at 100 microns depth with 50 opening. 0.1% riboflavin is instilled one time in that pocket for 2 mins Cross-links, 60 microns anterior to the pocket and 200 microns behind without having to remove the corneal epithelium
- 43. • Follow upof 4- 8 months • No endothelial damage • K value reduced by 1.7 D and MSE by 1.5
- 44. SANCHEZ-LEON MODIFIED TECHNIQUE FORLASIK ECTASIA Lasik flap edge is identified. Opened gently 100 using a Sinsky hook. IntraLase Lasik spatula is used to create an intra stromal pocket, leaving the rest of the margin of the flap intact. The 0.1% Riboflavin is instilled direct in to the stromal space.
- 46. OTHER USES • PMD– 11 mm area needs to be debrided, limbus protected. Single segment ICRS may have to be inserted • Stabilizing corneal flattening and hyperopia in post RK • PSEUDOPHAKIC BULLOUS KERATOPATHY – glycerol to de swell the cornea upto 400 microns • STERILE CORNEAL MELTS – resistence to digestive enzymes - low surface irradiation = 2.5 mW/cm2 because of thinning • INFECTIOUS CORNEAL ULCERS – e g acanthamoeba keratitis
- 47. CORNEOPLASTIQUES • Corneal reshapingtechniques without using invasive procedures like PKP and LK Mechanical -ICRS -incisions Elastic -Conductive keratoplasty -C3R LASER- Excimer – PRK / ASA • Modifying the shape first and then solidifying by C3R • Even in post PK / LK patients for reshaping the cornea • Basically managing high irregular astigmatism
- 48. • Combined withICRS and orthokeratology • Trans epithelial cross linking after ICRS
- 51. • Combined withTOPO GUIDED PRK (Kanellopoulos) min pachy at thinnest point = 450 microns better than wavefront guided prk persistent epithelial defects especially if mitomycin c is used 25 % under correction required C3R followed by PRK later more risk of scarring loss of cross linked tissue
- 52. CONCLUSIONS • Rapidly evolvingprocedure – Techniques – Indications – combinations • Main aim is to halt the/ delay the progress of ectasia postponing PKP by strengthen the lamellar fibres • LONG TERM STUDIES needed -durability of stiffening as Collagen turn over is known to occur in 2-3 years -serious late complications
- 53.