Photochemical corneal collagen cross‑linkage using riboflavin and ultraviolet A for keratoconus and keratectasia

In the studies included in the systematic review for epithelium‑off corneal collagen cross‑linkage (CXL), meta‑analysis of the change between preoperative and postoperative data for topography reported significant improvements in maximum keratometric values (max K) at 6, 12 and 24 months (-0.8 dioptres [D] at 6 months and -1.0 D at 12 and 24 months), and mean and minimum keratometric values (mean K and min K) at 12 months only (-1.0 D and -0.7 D for mean K and min K respectively).

Meta‑analysis results for visual acuity reported significant improvement in corrected visual acuity (CVA; -0.20 LogMAR) but not uncorrected visual acuity (UCVA) between intervention and control eyes on the LogMAR scale at 12 months follow‑up. Meta‑analysis of the change between preoperative and postoperative data showed significant improvements in UCVA postoperatively at 6, 12 and 24 months. Improvements on the LogMAR scale were in the order of -0.15 for UCVA and -0.10 for CVA at various time points.

Meta‑analysis results for astigmatism reported no significant differences between the treatment and control groups at 12 months (-1.42 D). Differences between preoperative and postoperative data showed significant improvements at 6, 12 and 24 months (-0.4 D at 6 months, -0.7 D at 12 months and -0.5 D at 24 months). Change in spherical equivalence (SE) was only significant at 12 months (there was a reduction of between 0.3 and 0.5 D).

Meta‑analysis of the change between preoperative and postoperative data showed a significant decrease (-14.4 micrometres) in central corneal thickness and no significant difference in intraocular pressure at 12 months follow-up.

A randomised controlled trial in 48 eyes with progressive keratoconus (43 patients) compared 2 sequences of combined CXL and intracorneal ring segment (ICRS) implantation with a mean interval between treatments of 7 months. Group 1 had epithelium‑off CXL followed by ICRS implantation and group 2 were treated by ICRS implantation followed by epithelium‑off CXL. The mean UCVA and corrected distance visual acuity (CDVA) had improved significantly in both groups 6 months after the procedures (each group gained 1 Snellen line in UCVA, and group 1 gained 1 line in CDVA but group 2 gained only half a line). The same study reported statistically significant improvements in the mean SE, cylinder and mean K values in both groups but there was more improvement in CDVA, SE (2.76 D versus 0.93 D), and mean K (3.3 D versus 1.1 D) in group 2 than in group 1.

A randomised comparative case series of 42 eyes (21 patients) with bilateral keratoconus and 50 micrometres of epithelium removed by photorefractive keratectomy (PRK) compared 2 levels of exposure to ultraviolet A (UVA; both eyes were treated with CXL). In both groups, mean uncorrected distance visual acuity improved, from 20/60 to 20/38 and from 20/62 to 20/40 Snellen lines respectively; CVA improved from 20/30 to 20/25 Snellen lines; mean SE was reduced by 2.5 D and 2.1 D; mean refractive cylinder was reduced by 2.9 D and 2.5 D; max K was reduced by 3.4 D and 2.9 D at 24 months.

A case series of 11 eyes (11 patients with progressive keratoconus) treated with CXL 6 months before phakic intraocular lens (PIOL) implantation and followed up 6 months after the PIOL implantation reported statistically significant improvement in mean UCVA (by 0.24 LogMAR 6 months after CXL, and by 1.24 LogMAR 6 months after PIOL) and CVA (by 0.02 LogMAR and 0.1 LogMAR at the 2 time points), reduction in mean K values (by 1.26 D and 2.14 D at the 2 time points), SE (by 0.45 D and 5.43 D at the 2 time points) and cylinder values (by 0.16 D and 0.55 D at the 2 time points).

A comparative case series of 51 eyes (51 patients with progressive keratoconus) treated with epithelium‑on (transepithelial) CXL reported improvements in mean CDVA (by 0.036 LogMAR for CXL versus 0.039 LogMAR for control, p<0.05), and reduction in mean K values (by 0.51 D after CXL versus 1.61 D for control, p>0.05) and SE (0.35 D after CXL versus 0.83 D for control, p<0.05) at 12 months follow-up.

A case series of 14 eyes (10 patients with mild to moderate keratoconus) treated with epithelium‑on (transepithelial) CXL and combined same-day corneal implants reported improvements in mean best corrected visual acuity (BCVA; from 0.24 LogMAR to 0.16 LogMAR, p=0.34), and mean K values (45.83 D to 44.03 D, p=0.0023) at 3 years follow‑up.

A case series of 21 eyes (13 patients) treated with ICRS implantation followed by CXL after a mean of 4 months reported improvements in mean UCVA and BCVA 6 months after CXL (UCVA from 0.05 to 0.23 LogMAR, p=0.951; BCVA from 0.18 to 0.41 LogMAR, p=0.08). The study also reported reductions in SE and cylindrical and mean keratometric values after ICRS implantation (2.8 D, p<0.05; 2.1 D, p<0.05; and 2.5 D, p<0.05 respectively) which were maintained 6 months after CXL.

The specialist advisers listed efficacy outcomes as arrest of progression of keratoconus and stabilisation of the corneal shape measured by topography, refraction and keratometry, refractive astigmatism, change in corneal thickness, cone apex power, quality of life and contact lens independence.