Arthur Cummings

Posted: Friday, October 2, 2015

 Comparative map before and after CXL-plus (trans-PTK-PRK + accelerated CXL). SCVA improved from 20/50 to 20/25


Epi-off corneal crosslinking (CXL) is a proven treatment for corneal ectatic disease. It halts the ectatic process by strengthening the cornea by means of creating covalent bonds between collagen fibrils. In the last three years many efforts have been made by researchers and ophthalmic companies to improve the quality and the time of treatment through development of new riboflavin solutions and new irradiance protocols.

However, even though the main target of halting corneal ectasia is reached in most cases, few patients affected by moderate to severe keratoconus have a consistent visual acuity (VA) improvement. When performed on its own, the CXL procedure is not intended to improve vision, but rather to stabilise disease, and therefore the patient still remains to be rehabilitated visually, thereby affecting their quality of life. Many face the need to wear customised contact lenses and the inability to improve spectacle corrected visual acuity (SCVA) is often frustrating for both patients and surgeons, especially considering the well-known problems of contact lens abuse such as corneal inflammation, erosions, infection, chronic intolerance and so on.

Corneal surgeons are therefore searching for techniques that, other than halting keratoconus, also improve corrected VA. Corneal shape regularisation is a key factor for improving the quality of vision and reducing aberrations, especially coma. For this reason, in 2011 the term ‘CXL-plus’ was introduced to describe several combined procedures that aimed at enhancing VA after CXL. Various combinations have been tried towards this goal.



CXL can be combined with the implantation of intrastromal rings. These have been proposed as simultaneous and sequential protocols. However, the result is not always predictable. Dr Miguel Rechichi from the Eye Centre Clinic, Catanzaro, Italy, who has extensive experience with CXL, says: “CXL-plus is a promising approach to improve VA and regularise corneal geometry. I think that an ectatic cornea can be treated in many ways but the challenge is in finding the best solution that improves corneal geometry without affecting corneal biomechanics. In my opinion it’s crucial to perform the two steps at the same time starting with the 'plus' procedure (intrastromal rings, laser ablation or both) for corneal regularisation followed by accelerated crosslinking to stiffen and ‘fix’ the reshaped cornea. Though I have, in general, good results using intrastromal rings, this is not my first choice because the refractive effect is not always completely predictable even with femtosecond-assisted implantation. I therefore started to look with greater interest at the excimer laser approach for corneal reshaping and have got very encouraging results.”



More recently CXL has been combined with the use of the excimer laser, which may be used for removal of epithelium (transepithelial phototherapeutic keratectomy, or t-PTK) or Cretan protocol, and the topography-guided photorefractive keratectomy (PRK) or Athens protocol.



Described by Kymionis et al, t-PTK is used to remove epithelium as well as to smoothen the anterior irregular stroma and decrease irregular astigmatism. Dr Rechichi says: “I had better results removing just epithelium with PTK (Cretan protocol) in corneas thinner than 400 micron. We know that epithelium is thinner over the cone so just removing 50 microns using epithelium as a masking agent by PTK, as suggested by Kymionis et al, improves corneal geometry, removing a limited volume of stromal tissue in the cone area.”



First described by Kanellopoulos et al, topography-guided partial PRK is used to regularise anterior corneal shape and decrease irregular astigmatism and is followed by CXL. It consists of a 6.5mm PTK to remove 50μm of epithelium followed by topography-guided partial PRK, application of mitomycin C (0.02 per cent for 20 seconds), and the CXL procedure. No more than 50μm of stroma is removed and up to 2.00-2.50D of astigmatism with up to 1.00D of myopia is treated.

Kanellopoulos et al also postulated that CXL in a PRK-treated eye may be biomechanically stronger as a crosslinked eye with a more regular surface and would likely remain more stable due to strain redistribution than an eye with localised ongoing strain at the cone’s peak. Simultaneous CXL also avoids removal of crosslinked corneal tissue as compared to sequential (CXL before excimer ablation).

Dr Rechichi says: “I used topography-guided partial PRK (Athens protocol) in corneas up to 470 microns keeping 50 microns as maximum depth of ablation and found it effective. Two years ago, when I and Dr Cosimo Mazzotta changed our refractive platform, we started using customised trans-PRK for corneal regularisation followed by accelerated pulsed CXL, and set up a fixed algorithm that we call STARE-XL (Selective Transepithelial Ablation for Regularisation of Corneal Ectasia Crosslinking) in patients with SCVA < 20/30 and age > 20 years. The basic steps of this algorithm are to use the central corneal thickness (CCT) and the thinnest corneal point for customisation of PTK-assisted removal of real epithelial map.”



Dr Rechichi says patients affected by medium to severe forms of keratoconus are focused on VA improvement and always ask the same question of him: ‘Doctor, will I see better after the treatment?’

“When I started with CXL alone more than eight years ago, my answer was: ‘The real target is stabilising the cornea, but we have some chance to improve SCVA in the mid- to long-term period after surgery.’ Now I say that we have a good chance of improving spectacle corrected VA in the medium term. (see Figure 1)

“The great aspect of this surgical approach is not only the quantitative improvement of vision but also the subjective improvement seen in the quality of vision as well as a significant decrease in aberrations,” says Dr Rechichi.


Dr Soosan Jacob is a Senior Consultant Ophthalmologist at Dr Agarwal’s Eye Hospital, Chennai, India, and can be reached at