Corneal collagen cross linking - ophthalmology

Ophthalmology topics

1.                                Corneal Collagen Cross-Linking [C3R]  By – Titiksha Sharma

2. Corneal collagen crosslinking (CXL) is a minimally invasive procedure used to prevent progression of corneal ectasia [ a group of conditions that cause your cornea to thin and bulge outward ] such as keratoconus and post-LASIK ectasia. WHAT I S MEANT BY CROSS LINKING? It’s the ability of collagen fibrils to form strong chemical bonds with adjacent fibrils  which occurs naturally with ageing due to oxidative deamination .  It has been hypothesized that this natural cross-linkage of collagen explains why keratectasia (corneal ectasia) often progresses most rapidly in adolescence or early adulthood but tends to stabilize in patients after middle-age. The primary purpose of cross-linking is to halt the progression of ectasia .     

3. The main components of CXL - 1) Photosensitizer 2) UV light source 3) Resulting photochemical reaction.

4. Riboflavin A photosensitizer  Absorbs light energy and produces a chemical change in another molecule. Absorbed by the corneal stroma topically. It has an absorption peak at 370 nm. [ 3] UV Light As the absorption peak of riboflavin was noted to be 370 nm, UV-A light was found to be ideal for CXL, while at the same time protecting the other ocular structures

5. Photochemical Reaction Once exposed to UV-A light, the riboflavin generates Reactive oxygen species, which induce the formation of covalent bonds both between collagen molecules and between collagen molecules and proteoglycans Oxygen Recent studies indicate that the presence of oxygen is essential for effective CXL

6. Indications- best candidate for this therapy is an individual with a progressive ectatic disease of the cornea. Note that it's not a definitive treatment it only halts progressio n .  Keratoconus Pellucid Marginal Degeneration Terrien Marginal Degeneration Post-refractive surgery (such as LASIK, PRK, or Radial Keratotomy) ectasia Infective Keratitis – in cases resistant to standard antimicrobial therapy. Bullous keratopathy -to cause reduction in corneal oedema.    Parameters to consider- Are change in refraction (including astigmatism) Uncorrected visual acuity Best corrected visual acuity Corneal shape (topography and tomography).

7. Surgical Technique-   The standard treatment protocol, called the Dresden protocol , for corneas with minimal thickness of 400µm, and is as follows: Instill topical anesthetic drops in the eye Debride the central 7-9mm of corneal epithelium Instill 0.1% riboflavin 5-phosphate drops and 20% dextran solution every 5 minutes for 30 minutes Exposure to UVA (370nm, 3mw/cm 2 ) for 30 minutes while continuing instilling the above drops every 5minutes. At the end of the procedure, apply topical antibiotics and soft BCL [ BANDAGE CONTACT LENS ] with good oxygen permeability.

8. In the video shown, anesthetic drops are given, then the speculum is placed and the epithelium is removed. Next, drops of riboflavin are administered, followed by UV exposure.

9. Variations in Surgical Technique Variations in Riboflavin Delivery Epithelium-off method - most commonly used for better penetration of riboflavin  As the corneal epithelium offers a barrier.  Epithelium-on method / Trans-epithelial method -   use of pharmacological agents to loosen the intraepithelial junctions, the creation of intrastromal pockets for direct introduction of riboflavin, and iontophoresis. Even though debridement induced complications like postoperative pain and corneal haze are avoided, studies thus far have demonstrated lower effectiveness of CXL in this method. [5] Osmolarity Hypo-osmolar riboflavin is used in thin corneas with a thickness between 400 and 320 µm to thicken the cornea to a minimum of 400 microns. [6] Variations in UV Exposure Treatment Time - Accelerated CX L Several protocols have been tried to reduce the treatment time by increasing the intensity of UV exposure

10. Healing of epithelial defect - 3-5 days 1)Bandage contact lens / patching 2)Cycloplegics, antibiotic, NSAID & artificial tears eye drops 3)Oral analgesic SOS • Mild steroid eye drops for 3-6 weeks (FML 0.1%) Review at 1 week, 4 weeks, 12 weeks, 24 weeks and 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 TREATMENT  - POST OP

11. . Contraindications Corneal thickness of less than 400 microns  Prior herpetic infection as it may result in viral reactivation Concurrent infection Severe corneal scarring or opacification History of poor epithelial wound healing Severe ocular surface disease (ex. dry eye) Autoimmune disorders

12. Complications Temporary stromal edema Temporary haze and permanent haze  Corneal scarring and sterile infiltrates Infectious keratitis: Bacterial/protozoan/herpetic  Diffuse lamellar keratitis (DLK) in a post-LASIK patient SPECIAL SITUATIONS KIDS-SAFE & STRAIGHT AWAY THIN CORNEAS HYPO-OSMOLAR OR HIGHER CONC. RIBOFLAVIN PREGNANCY OBSERVE / CXL CONTRAINDICATED

13. Thank you