**Abstract**

Biomechanical reinforcement of the cornea by collagen cross-linking (CXL) using riboflavin and ultraviolet A (UV-A) irradiation is a well-established treatment for halting the progression of keratoconus. Corneal pachymetry is one of the most important factors with respect to the safety of CXL. In addition to the initial pachymetric changes, significant changes in corneal pachymetry may occur during the different steps of the procedure, highlighting the role of intraoperative pachymetric measurements. Intraoperative optical coherence tomography (OCT) can be used safely and effectively to monitor the corneal pachymetry during CXL. Among the advantages of this technology is its ability to provide a more detailed profile of the corneal thickness in a noncontact manner compared to the ultrasound method. These features are especially advantageous for monitoring corneal pachymetry in the setting of CXL in KCN patients, considering the marked irregularity of the epithelium and stroma in these patients. OCT has also been used for evaluation of other aspects of the CXL procedure like evaluation of in vivo riboflavin penetration in to the corneal stroma.

**Keywords:** anterior segment OCT, keratoconus, collagen cross-linking, intraoperative OCT, corneal pachymetry

## **1. Introduction**

Keratoconus is a bilateral, progressive, ectatic disease characterized by progressive corneal thinning and irregular astigmatism. Biomechanical instability of the cornea is considered a main feature contributing to disease manifestations and a hallmark of this disease [1].

Biomechanical reinforcement of the cornea by collagen cross-linking (CXL) using riboflavin as a photosensitizer and ultraviolet A (UV-A) irradiation is a wellestablished treatment for halting the progression of keratoconus [2, 3].

The CXL process is mediated by a photo-oxidation reaction between UV-A (370 nm) and riboflavin (vitamin B2). Reactive oxygen species produced during this reaction, including singlet oxygen, react with the collagen fibril molecules in corneal stroma and enhance the mechanical strength of cornea by forming new chemical bonds between collagen fibril molecules [4].

The original procedure (Dresden protocol) includes removal of the central 7 mm of the corneal epithelium (epithelium-off method), riboflavin saturation of the

stroma with 0.1% riboflavin-20% dextran solution (every 5 minutes until 30 minutes), and then application of UV-A light source (370 nm with irradiance of 3 mW/ cm2 ) on the cornea for 30 minutes [2]. However, there have been other modifications such as preserving the corneal epithelium (epithelial-on method), increasing the intensity of the UV source and decreasing the irradiation time (accelerated method), and using a continuous versus a pulsed light source after the description of the original procedure.

A significant increase up to 71.9 and 328.9% in corneal rigidity has been demonstrated in experimental studies in porcine and human corneas, respectively [4], and long-term studies have demonstrated the safety and efficacy of CXL in halting the progression of keratoconus [5, 6].

### **2. Significance of corneal pachymetry as a safety criteria for CXL**

Corneal thickness (measured by pachymetry) is one of the most important factors with respect to the safety of CXL; a minimum thickness of 400 μm is recommended to ensure the safety of the procedure and avoid the potential toxic effects of UV-A irradiation on the corneal endothelium [7]. Both an adequate corneal thickness and adequate riboflavin saturation of the cornea are necessary to ensure photochemical damage caused by the free radicals to the corneal endothelium.

With the currently used irradiation doses in CXL (UV-A radiant exposure of 5.4 mJ/cm2 and the corresponding irradiance of 3 mW/cm<sup>2</sup> ), the estimated level of irradiance at a depth of 400 μm is 0.18 mW/cm2 which is by two factors below the damage threshold [7].

CXL in thin corneas with a minimum corneal thickness below 400 μm after epithelial removal has been reported to result in significant endothelial cell loss postoperatively, emphasizing the role of corneal pachymetry as a critical factor for the CXL procedure [8].
