Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Summary

Corneal collagen cross-linking (CXL) is the only conservative treatment currently available to halt keratoconus progression by improving the biomechanical rigidity of the corneal stroma. The aim of this manuscript is to highlight the methods of three different protocols of CXL: conventional CXL (C-CXL), accelerated CXL (A-CXL), and iontophoresis CXL (I-CXL).

Abstract

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been introduced as an efficient treatment option. In biological and chemical sciences, crosslinking refers to new chemical bonds formed between reactive molecules. Hence, the aim of corneal collagen CXL is to synthetically increase the formation of crosslinks between collagen fibrils in the corneal stroma. Despite the fact that the efficiency of the conventional CXL (C-CXL) protocol has already been shown in several clinical studies, it might benefit from improvements in duration of the procedure and removal of corneal epithelium. Hence, in order to provide a coherent evaluation of two new and optimized CXL protocols, we studied keratoconus patients who had undergone one of the three CXL treatments: iontophoresis (I-CXL), accelerated CXL (A-CXL), and conventional CXL (C-CXL). A-CXL is a 6 time faster CXL procedure using a ten time higher UVA irradiance but still including an epithelium removal. Iontophoresis is a transepithelial non-invasive technique in which a small electric current is applied to improve riboflavin penetration throughout the cornea. Using anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy (IVCM), we conclude that regarding the depth of treatment penetration, conventional CXL protocol remains the standard for treating progressive keratoconus. Accelerated CXL seems to be a quick, effective and safe alternative to treat thin corneas. The use of iontophoresis is still being investigated and should be considered with greater caution.

Introduction

Keratoconus is a bilateral and progressive corneal ectasia usually reported in 1 in 2,000 in the general population¹ resulting in modification of the corneal shape and thus decreased vision². Keratoconus is usually present in early puberty and progresses until the third to fourth decade of life when the disease typically tends to stabilize, although progression can be variable throughout a patient's life. By halting keratoconus progression, cross linking aims at postpone or avoid keratoplasty.

To date, the only efficient and safe treatment of progressive keratoconus proven in clinical studies is the conventional co....

Protocol

These protocols follow the guidelines of our institution's human research ethics committee.

1. Conventional Corneal Collagen CXL (C-CXL)

1. Preparation of the Patient

1. 5 days before the surgery, put 1% pilocarpine drops twice a day in the treated eye.
2. In the operating room, in aseptic conditions, lie the patient on his/her back.
3. Administer topical anesthesia such as oxybuprocaine 0.4%.
4. Clean the eye and the skin around the eye with iodine antiseptic twice.
5. Use a lid speculum to keep the eye open.

2. Epithelial Removal

Discussion

CXL using UVA irradiation and riboflavin is the standard treatment for arresting the progression of keratoconus. Riboflavin is a photosensitizer which induces chemical covalent bonds (cross-links) when irradiated with UVA³. In the cornea, this phenomenon creates cross-links between collagen fibrils that increase corneal stiffness. Although this phenomenon is well described, until now there has been no direct evidence of intracorneal cross-links. Nonetheless, several studies have reported a stabilization of the.......

Materials

Name	Company	Catalog Number	Comments
		Riboflavin        Product number
C-CXL	Sooft SPA, Montegiorgio, Italy	Ricrolin                        468465-6
A-CXL	Avedro Inc, Waltham, Massachusetts	VibeX                              520-01863-006
I-CXL	Sooft SPA, Montegiorgio, Italy	Ricrolin+                      975481-6	Passive electrode: PROTENS ELITE 4848LE/ Active electrode: IONTOFOR CXL
		UVA Machine
X-Vega			UVA: 3 mW/cm2 30 min
KXL System			UVA: 30 mW/cm2 10 min
X-Vega			UVA: 10 mW/cm2 9 min