| Study | Study design/ Protocol | No. of Eyes | Follow-up, months | Criteria for Progression | UV device/ UV energy/ Riboflavin | Outcome | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| – | – | – | – | – | – | Overall | Pre-op K (D) | ΔK (D) | ΔUCVA | ΔBCVA | Δ Refraction (D) |
| Soeters et al, 2015 [42] | Randomised clinical trial/ 3mW/cm2 30 min | 61; 35 epi-on, 26 epi-off | 12 | ↑ Kmax, Ksteep, mean K and/or topographic cyl value by ≥ 0.5D/6-12 months | For both: UV-X; Peschke Meditrade Epi-on: 0.1% riboflavin with 15.0% dextran, trometamol and EDTA Epi-off: isotonic riboflavin 0.1% solution with 20% dextran |
Average Kmax remained stable for the epi-off group but showed significant flattening in the epi-off group. CDVA showed a better outcome in the epi-on group. | Kmax (epi-off): 57.8 ± 7.1 Kmax (epi-on): 56.4 ± 5.0 |
Epi-off: -1.5 ± 2.0 Epi-on: +0.3 ± 1.8 (P = 0.022) |
Epi-off: -0.15 ± 0.43 (LogMAR) Epi-on: -0.06 ± 0.37 (LogMAR) (P = 0.591) |
Epi-off: -0.07 ± 0.21 (LogMAR) Epi-on: -0.14 ± 0.21 (LogMAR) (P = 0.023) |
SE (Epi-off): +0.4 ± 3.0 SE (Epi-on): +0.3 ± 1.6 (P = 0.436) |
| Al Fayez et al, 2015 [41] | Prospective clinical trial/ 3mW/cm2 30 min | 70; 34 epi-on, 36 epi-off | 36 | ↑ max K/ manifest astigmatism ≥ 1D/12 months | Epi-on: IROC/ 1% tetracaine/ 0.02% benzalkonium chloride, dextran-free riboflavin Epi-off: IROC/ 0.1% riboflavin with dextran 20% solution 30 min |
Kmax decreased in the epi-off group but increased in epi-on group. | - | Kmax (epi-off): -2.4 Kmax (epi-on): +1.1 (P < 0.0001) |
Epi-off: -0.2 (LogMAR) Epi-on: +0.1 (LogMAR) (P < 0.0001) |
Epi-off: -0.1 (LogMAR) Epi-on: +0.06 (LogMAR) (P = 0.055) |
- |
| Filippello et al, 2012 [37] | Prospective case-control cohort study/ 3mW/cm2 30 min | 40; 20 epi-on, 20 FE control | 18 | 1. ↑ max cone apex curvature ≥ 1D/6 months 2. ↓ corneal thickness > 2%/6 months 3. ↑ central corneal astigmatism ≥ 1D/6 months |
Vega/ 0.1% riboflavin with dextrane T500, trometamol and EDTA sodium salt | Improved UCVA and CVA, topography-derived keratometry, cone apex power, and HOA. | SIM K steepest (treated): 51.02 ± 1.10 SIM K steepest (FE control): 51.12 ± 1.02 |
Treated: From 51.02 ± 1.10 to 48.05 ± 0.21 FE control: 51.12 ± 1.02 to 52.12 ± 0.47 (P < 0.05) |
Treated: From 0.71 ± 0.12 to 0.48 ± 0.34 (LogMAR) FE control: From 0.84 ± 0.23 to 0.98 ± 0.41 (LogMAR) (P < 0.05) |
Treated: From 0.35 ± 0.23 to 0.24 ± 0.77 (LogMAR) FE control: From 0.46 ± 0.21 to 0.64 ± 0.39 (LogMAR) (P < 0.05) |
- |
| Leccisotti et al, 2010 [47] | Prospective, consecutive, single-masked, paired-eye study/ 3mW/cm2 30 min | 102; 51 treated, 51 FE control | 12 | Myopia/ astigmatism ↑ 1D or average SIM K ↑ 1.50D/12 months | CBM Vega X-linker/ 0.1% riboflavin with 20% dextran T500 and oxybuprocaine | Improved mean CDVA, decreased mean SE refraction, reduced increase of mean apex curvature, decreased mean average simulated K, reduced increase of mean index of surface variance. | Mean average SIM K (treated): 46.63 ± 2.89 Mean average SIM K (control): 44.60 ± 2.19 |
Treated: -0.10 ± 1.44 Control: 0.88 ± 2.35 (P < 0.05) |
- | Treated: -0.036 ± 0.049 (LogMAR) Control: +0.039 ± 0.032 (LogMAR) (P < 0.05) |
Mean SE (treated): +0.35 ± 0.66 Mean SE (control): -0.83 ± 0.88 (P < 0.05) |
| Vinciguerra et al, 2014 [44] | Prospective non-randomised clinical study/ 10mW/cm2 9 min | 20 | 12 | 1. Δ curvature in cone area of ≥ 1D 2. Thinning of > 20μm in minimal Scheimpflug corneal thickness |
UV-X 2000; IROC/ 0.1% riboflavin, with EDTA and trometamol, dextran-free or sodium chloride administered by iontophoresis (I-ON XL, SOOFT) | Improved CDVA. Aberrometry remained stable and a trend towards improvement. No progression of keratoconus. | Max K: 59.07 ± 3.90 | -0.549 ± 2.344 (P = 0.40) | - | -0.12 ± 0.06 (LogMAR) (P = 0.01) | SE: +1.117 ± 3.783 (P = 0.20) |
| Koppen et al, 2012 [48] | Prospective cohort study/ 3mW/cm2 30 min | 53 | 18 | 1. ↑ max K ≥ 1D 2. ↓ visual acuity and refraction |
Vega CBM X-linker/ 0.1% riboflavin in 20.0% dextran | Only corrected distance visual acuity showed significant improvement. Maximum K and pachymetry at the thinnest point continued to progress. | SIM K steepest: 48.69 ± 5.39 | +0.48 ± 0.28 (P > 0.05) | - | +0.05 ± 0.03 (SDE) (P > 0.05) | Sphere: + 0.04 ± 0.21 (P > 0.05) Cyl: -0.08 ± 0.19 (P > 0.05) |
| Caporossi et al, 2013 [40] | Prospective case series/ 3mW/cm2 30 min | 26 | 24 | 1. ↓ UDVA and/or CDVA > 1 Snellen line 2. ↑ sphere and/or cyl > 0.50 D 3. ↑ topographic symmetry index surface asymmetry index and/or symmetry index > 0.50D 4. ↑ max K > 1D 5. ↓ thinnest point on AC OCT ≥ 10μm |
CBM X-linker, VEGA/ 5.4J/cm2/ 0.1% riboflavin with 15.0% dextran, trometamol and EDTA | UDVA and CDVA improved in the first 3-6 months but returned to baseline. Simulated maximum K value worsened at 24 months. Spherical aberration increased at 24 months. | Max K: 48.59 | +1.55 (P = 0.05) | -0.05 Snellen lines (P = 0.61) | +0.05 Snellen lines (P = 0.57) | - |
| Bikbova et al, 2014 [43] | Prospective case series/ 3mW/cm2 30 min | 22 | 12 | 1. ↑ steepest K by ≥ 1D in manifest cyl 2. ↑ ≥ 0.5D in manifest SE |
UFalink/ Riboflavin 0.1% solution administered by iontophoresis (Potok-1) | Decreased average K level, corneal astigmatism. Improved UDVA. | Max K: 47.82 ± 2.23 | From 47.82 ± 2.23 to 45.72 ± 2.13 | From 0.61 ± 0.44 to 0.48 ± 0.41 | From 0.34 ± 0.29 to 0.29 ± 0.25 (LogMAR) (P > 0.062) | Cyl: From 3.44 ± 0.48 to 2.95 ± 0.23 |