Corneal Cross-Linking - Guideline

Indication for Corneal Cross-Linking (CXL)

• Progressive ectatic disease of the cornea
  • Keratoconus
  • PMD
  • Ectasia after refractive laser surgery (PRK/LASIK/lenticule extraction)

• Definition of progression on topography/tomography
  • Kmax =/> +1 D within 6 months
  • Posterior float: increase within 6 months
  • Pachymetry: decrease > 10 µm within 6 months

• Evidence of progression based on old spectacle prescriptions or a history of decreased visual acuity is sufficient for prompt planning of CXL
  • Young patients < 25 years
  • Atopy/allergy/patients who frequently rub their eyes (rubbers)

Preparation

• Application for cost coverage
• Topography/tomography (Pentacam), endothelial cell count
• Informed consent -> see consent form for pterygium excision (incl. infection/scarring/postoperative pain and inability to work for at least 1-2, up to 4 weeks)
• Preoperative preparation
  • Oxybuprocaine 0.4% eye drops 3x every 5 minutes

Surgical Materials

• Secure the UV device firmly to the edge of an instrument table with a clamp, plug in the cable safely, calibrate if necessary
• Pachymeter: insert batteries and switch on
• Hockey knife

Disposable Materials

• Hibidil® solution
• Round swabs x6
• Sterile drape
• Disposable film scissors
• Bangerter lid speculum
• BSS solution in a 10 ml syringe with a blunt cannula
• Sterile distilled water in a 10 ml syringe with a blunt irrigation cannula
• Lidocaine 2% solution
• Riboflavin 0.1% HPMC solution (e.g. VibeX Rapid®)
• Triangular swabs
• Bandage contact lens
  • Soaked in Dexafree eye drops 2x and Floxal eye drops 2x for at least 30 minutes
• Floxal eye ointment

Surgical Procedure

Topical anesthesia. Disinfection. Sterile draping.
Corneal abrasio using the hockey knife.
+PLUS (self-pay service): topography-/aberrometry-guided PTK/transPTK.
Ultrasound pachymetry. Preparation of the stroma for 20 minutes by alternating application of riboflavin solution and distilled water every two minutes. Oxybuprocaine eye drops every five minutes.
Irradiation with UVA according to the respective protocol
‍+PLUS (self-pay service): customized protocol
Rinsing of the cornea with BSS solution. Floxal eye ointment applied to the cornea, 2 mm ointment strand. Insertion of the loaded bandage contact lens. Application of a monocular patch with light pressure.

caution: 

• working distance from the UVA source to the corneal apex = 50 mm -> the irradiated area is sharply demarcated
• the irradiated area should be centered over the pupil center, or slightly decentered according to the location of the keratoconus (usually nasal-inferior); do not irradiate the limbus
• the patch must be applied with light pressure so that the patient cannot blink under the patch

Surgical Protocols

• Standard at ONO: Accelerated Protocol
  • Riboflavin application 20 min,
  • Intensity 9 mW/cm²
  • Treatment duration 10 min
• PRK+CXL
  • Accelerated Protocol (see above)
  • Topography-guided PRK
• sub400 Protocol (pachymetry 200-400 µm)
  • Treatment duration is adjusted to corneal thickness
  • Settings
    • Intensity 3 mW/cm²
    • Epi-off
    • Chromophore 0.1% riboflavin, swelled with distilled water
    • Irradiation mode: continuous
    • UV source: CXL-365
    • Treatment time depends on pachymetry

Postoperative

Analgesia (caution: adjust if necessary for body weight and liver/kidney values)

• Paracetamol 500 mg tablet 4x/day up to 8x/day (e.g. Dafalgan®)
• Non-steroidal anti-inflammatory drug (e.g. mefenamic acid 500 mg tablet 3x/day or ibuprofen 400 mg tablet 4x/day)
• As needed: opioid analgesic (e.g. Tramal retard® 100 mg tablet 2x/day (dispense 4x) (maximum 400 mg/day)

Management

• 4 days: remove contact lens if applicable (caution: carefully, from inferior with a cotton-tipped applicator or with fine anatomical forceps from the temporal side, patient looks nasally)
  • Abrasion re-epithelialized: start with FML eye drops 4x/day for 1 week, 3x/day for 1 week, 2x/day for 1 week, 1x/day for 1 week
  • Persistent erosion: follow-up every two days until complete epithelial closure, only then start FML eye drops
  • Showering possible again, no water or shampoo in the eye, do not rub, eye shield at night
• 2 weeks
  • Corneal OCT central volume scan (measuring the depth of the demarcation line, given as a percentage of total corneal thickness, e.g. 80%)
  • No sauna/steam bath/swimming pool/diving underwater
• 1 month
  • Topography, corneal OCT (only for documentation if haze/scarring present)
  • Subjective visual acuity
  • If haze present, increase FML eye drops again to 4x/day for 2 weeks -> follow-up with corneal OCT
    • taper over 8 weeks (3x/day for 2 weeks, etc.)
  • All activities possible again
  • if applicable, clear patient for fitting of rigid gas-permeable contact lenses (prescription with MiGel position 25.02.03.00.1)
• 4 months
  • Topography, corneal OCT (only for documentation if haze/scarring present)
  • Subjective visual acuity
  • If late-onset haze present, increase FML eye drops again to 4x/day for 2 weeks -> follow-up with corneal OCT, taper over 8 weeks (3x/day for 2 weeks, etc.)
  • If the cornea has cleared and there is existing progression of ectasia in the fellow eye -> CXL on the fellow eye

FAQs

Should CXL be performed early in young patients with early keratoconus?

Patients aged 14-25 years -> ectasia (keratoconus) can progress rapidly

• In patients who frequently rub their eyes -> start antiallergic medication
  • Opatanol eye drops 2x/day and Telfast 120 mg tablet 1x/day
• Follow-up with topography after 3 months
  • If progression -> case conference -> CXL

Should an eye with progressive ectasia but still very good best-corrected visual acuity be treated with CXL?

Yes, because the refractive error will soon no longer be correctable due to progressive corneal bulging. This can be prevented by stopping the progression.

Do rigid gas-permeable contact lenses help stop the progression of keratoconus?

No, this is a misconception. Keratoconus continues to progress underneath the contact lens.

Contact lens removal before topography

Rigid gas-permeable contact lenses can distort the epithelium and thus the topography -> contact lens removal for 1 week for soft lenses and 2 weeks for rigid lenses.
If this is not feasible for the patient because visual acuity cannot be adequately corrected with spectacles:

• Separate follow-up visits for each eye with the same lens-free period
• Reduce the lens-free period to at least 3 days (e.g. Friday to Monday, follow-up on Monday), if necessary certify inability to work

Can thin corneas be treated?

Yes. Thanks to the sub400 protocol, corneas with pachymetry down to 200 µm can be treated. For this, the intensity is reduced to 3 mW/cm² (as in the Dresden protocol) and, for example at 200 µm (thinnest location), irradiation is applied for only one minute (see above).

When does CXL no longer make sense?

As soon as dense stromal opacities appear and visual acuity can no longer be corrected to above 0.5 even with a pinhole or rigid gas-permeable contact lenses. In these cases, vision can only be rehabilitated by keratoplasty.