Superior outcome of corneal collagen cross‐linking using riboflavin with methylcellulose than riboflavin with dextran as the main supplement

Abstract

Purpose To compare the effect of corneal collagen cross‐linking (CXL) on progressive keratoconus using 0.1% riboflavin with either dextran or methylcellulose as the main supplement. Methods In a comparative case series, CXL was performed in 40 patients (40 eyes) using a riboflavin solution containing either dextran (dextran–riboflavin; n = 20) or methylcellulose (methylcellulose–riboflavin; n = 20). Changes in central corneal thickness (CCT), Scheimpflug tomography, maximal keratometry reading (Kmax), visual acuity (VA) and endothelial cell density (ECD) were recorded. Stromal changes one month after surgery were analysed using optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). Results The CCT was significantly higher in the methylcellulose–riboflavin group during the CXL procedure. The IVCM demarcation line depth was 274 ± 80 (SD) μm in the dextran–riboflavin group and 442 ± 80 μm in the methylcellulose–riboflavin group (p < 0.001). Complete absence of keratocytes in the pre‐endothelial stroma was found in none of the corneas treated with dextran–riboflavin and in 42% of the corneas treated with methylcellulose–riboflavin. Visibility of the OCT demarcation line was significantly lower in the methylcellulose–riboflavin group. Kmax and corrected distance visual acuity were improved in the methylcellulose–riboflavin group and stable in the dextran–riboflavin group after 2 years. Endothelial cell density (ECD) was stable in both groups. Conclusion We found deeper structural changes in the methylcellulose–riboflavin group than in the dextran–riboflavin group. This may be explained by different riboflavin solution properties and raises safety concerns. The study also indicates improved effect using methylcellulose–riboflavin than dextran–riboflavin, possibly explained by deeper stromal CXL effect.

<p>Comparative Two-Photon Fluorescence Microscopy Analysis of Riboflavin Penetration in Two Different Solutions: Dextran and Hydroxypropyl Methylcellulose</p>

“…Thorsrud et al demonstrated that HPMC riboflavin has faster diffusion than dextran riboflavin. 22 HPMC riboflavin allows a shorter procedure time than the Dresden protocol; thus, our study favors the current tendency to decrease the total procedural time of corneal crosslinking.…”

Accelerated corneal crosslinking with 20′-soaking hydroxypropyl methyl cellulose/riboflavin vs conventional crosslinking with 30′-soaking dextran/riboflavin

“…Ehmke et al demonstrated similar but not identical riboflavin gradients when comparing riboflavin in 1.1% HPMC applied for 10 minutes and riboflavin in 20% dextran applied for 30 minutes. 15 In the first 100 μm of the cornea, riboflavin/HPMC concentration was slightly lower in the HPMC group. However, after 200 μm corneal depth, riboflavin/HPMC concentration gradually increased and reached concentrations higher than those of the dextran group.…”

“…[10][11][12][13][14] Thorsrud et al showed, however, that a C-CXL protocol using a 20-minute imbibition of hydroxypropyl methyl cellulose (HPMC) produced a deeper DL on confocal microscopy and a significantly flatter maximum keratometry (Kmax) than C-CXL riboflavin with dextran. 15 A further point to note about the CXL reaction is the concentration of stromal riboflavin after soaking. A study by Ehmke et al performed on porcine eyes showed that a 10-minute soaking time with riboflavin 0.1% in a HPMC solution gave a relatively similar total concentration gradient to a 30-minute imbibition with dextran as the riboflavin's carrier agent.…”

“…10–14 Thorsrud et al showed, however, that a C-CXL protocol using a 20-minute imbibition of hydroxypropyl methyl cellulose (HPMC) produced a deeper DL on confocal microscopy and a significantly flatter maximum keratometry (Kmax) than C-CXL riboflavin with dextran. 15…”

Demarcation Line Depth in Epithelium-Off Corneal Cross-Linking Performed at the Slit Lamp

“…One factor that does affect demarcation line depth is the vehicle used in riboflavin solutions. In general, hydroxypropyl methylcellulose (HPMC)-based riboflavin solutions result in deeper riboflavin penetration and demarcation line depth as compared to dextran solutions [ 16 ]. It is worth noting, however, that HPMC-based riboflavin solutions display greater variability in demarcation line depth when used with a 9 mW/cm²/10 min irradiation protocol, such as that reported by Pircher et al (200 ± 99.76 µm) [ 10 ], when compared with dextran-based riboflavin solutions that display considerably lower variability in demarcation line depth (e.g., 203 ± 45 µm and 209 ± 50 µm found by Ng and colleagues [ 9 ]; 288 ± 42 µm by Kymionis and colleagues [ 12 ], and 265 ± 40 µm by Thorsrud et al [ 16 ].…”