| Study | Study design/ Indication/ Protocol | No. of Eyes | Follow-up, months | Criteria for Progression | UV device/ Riboflavin | Protocol | Outcome | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| – | – | – | – | – | – | – | Overall | Pre-op K (D) | ΔK (D) | Δ UCVA | Δ BCVA | Δ Refraction (D) |
| Kanellopoulos, 2012 [51] | Prospective, randomised bilateral comparison trial/ Keratoconus | 42; 21 Group A (treated), 21 Group B (FE control) | 18-56 (mean 46) | K > 45 and/or inferior steepening > 1D to the superior half of the cornea and 1D of tomographic cyl progression/ 1 year |
-/ 0.1% riboflavin 5 min | Group A: 7mW/cm2 15 min Group B: 3mW/cm2 30 min |
Improved UDVA and BCVA in both groups. Reduced mean sphere, mean cyl and steepest K. | - | Group A: 49.5 to 46.1 Group B: From 48.7 to 45.8 |
Group A: From 20/60 to 20/38 Group B: From 20/62 to 20/40 |
Both groups: From 20/30 to 20/25 | SE (Group A): -2.5 SE (Group B): -2.3 |
| Shetty et al, 2015 [56] | Prospective randomised interventional study/ Keratoconus | 138; 36 Group 1, 36 Group 2, 33 Group 3, 33 Group 4 |
12 | ↑ steep K by > 1.0-1.5D, a corresponding Δ (>1.0-1.5D) in subjective refraction or a ↓ ≥ 5% in thinnest pachymetry/ 6 months | Avedro KXL/ 0.1% riboflavin with 20% dextran 30 min | Group 1: 3mW/cm2 30 min Group 2: 9mW/cm2 10 min Group 3: 18mW/cm2 5 min Group 4: 30mW/cm2 3 min |
Improved mean CDVA and SE in all groups except Group 4, with Group 3 showing the best results. Flattening of steep and flat K was significant in Groups 1 and 2. Groups 1 and 2 showed a good demarcation line. | Steep K (Group 1): 50.5 ± 4.2 Steep K (Group 2): 49.9 ± 3.8 Steep K (Group 3): 48.6 ± 3.5 Steep K (Group 4): 49.4 ± 4.2 (P = 0.23) |
Group 1: 1.32 (P < 0.001) Group 2: 0.67 (P < 0.006) Group 3: 0.52 (P < 0.03) Group 4: -0.18 |
- | Group 1: 0.04 (SDE) (P < 0.05) Group 2: 0.06 (SDE) (P < 0.05) Group 3: 0.10 (SDE) (P < 0.05) Group 4: 0.02 (SDE) (P < 0.05) |
Group 1: -0.85 (P < 0.01) Group 2: -1 (P < 0.01) Group 3: -1.68 (P < 0.01) Group 4: -0.49 (P = 0.12) |
| Sherif, 2014 [58] | Prospective randomised interventional case-control clinical trial/ Keratoconus | 25; 14 accelerated, 11 conventional | 12 | ↑ ≥ 1.0D in steepest K, ↑ ≥ 1.0D in manifest cyl, or ↑ ≥ 0.5D in MRSE/ 6 months | 0.1% riboflavin with dextran 30 min | Accelerated: 30mW/cm2 4min 20s Conventional: 3mW/cm2 30 min |
Decreased flat K, steep K and mean K in both groups. Improved BSCVA. | Max K (accelerated): 49.43 ± 1.63 Max K (conventional): 51.4 ± 1.69 |
Accelerated: From 49.43 ± 1.63 to 48.2 ± 1.43 (P = 0.022) Conventional: From 51.4 ± 1.69 to 50.24 ± 2 (P = 0.099) |
- | Accelerated: From 0.48 ± 0.17 to 0.61 ± 0.15 (SDE) (P=0.015) Conventional: From 0.49 ± 0.19 to 0.64 ± 0.16 (SDE) (P = 0.03) |
- |
| Ng et al, 2016 [59] | Comparative interventional study/ Keratoconus | 26; 12 accelerated, 14 conventional | 14 | ↑ >1D in Kmax, ↑ >1D in manifest cyl or ↑ >0.5D in SE over 6-12 months |
Conventional: UV-X 1000, IROC/ Accelerated: UV-X 2000, IROC For both: Isotonic 0.1% riboflavin with 20% dextran solution 25 min |
Accelerated: 9mW/cm2 10 min Conventional: 3mW/cm2 30 min |
Conventional: improved CDVA, reduced Kmax, Kmean. Accelerated: unchanged CDVA, Kmax, Kmean |
Kmax (conventional): 53.5 ± 6.3 Kmax (accelerated): 51.6 ± 4.0 (P = 0.820) |
Conventional: -1.8 ± 1.8 Accelerated: -0.3 ± 0.9 (P = 0.015) |
- | Conventional: -0.126 ± 0.194 (LogMAR) Accelerated: 0.021 ± 0.092 (LogMAR) (P = 0.060) |
SE (conventional): 0.23 ± 0.87 SE (accelerated): 0.98 ± 3.81 (P = 0.796) |
| Chow et al, 2015 [60] | Prospective, interventional clinical study/ Keratoconus | 38; 19 accelerated, 19 conventional | 12 | ↓ ≥ 2 lines of BCVA + ≥ 1 of the following/ 12 months: 1. ↑ ≥ 1D in steepest K 2. ↑ ≥ 1D in astigmatism |
Conventional: UV-X, IROC Accelerated: CCL-Vario, Peschke Trade GmbH For both: 0.1% riboflavin with 20% dextran solution 30 min |
Accelerated: 18mW/cm2 5 min Conventional: 3mW/cm2 30 min |
Improved UCVA and BCVA, reduction in SE in both groups. A more effective topographic flattening was observed in conventional CXL. | Max K (conventional): 54.93 ± 1.72 Max K (accelerated): 51.96 ± 1.80 (P = 0.235) |
Conventional: -1.6 ± 0.72 Accelerated: -0.47 ± 0.83 (P = 0.343) |
Conventional: -0.28 ± 0.08 (LogMAR) Accelerated: -0.20 ± 0.06 (LogMAR) (P = 0.508) |
Conventional: 0.00 ± 0.04 (LogMAR) Accelerated: -0.14 ± 0.02 (LogMAR) (P = 0.430) |
SE (conventional): -1.3 ± 0.53 SE (accelerated): -0.57 ± 0.26 (P = 0.554) |
| Hashemian et al, 2014 [61] | Prospective clinical trial/ Keratoconus | 153; 77 accelerated, 76 conventional | 15 | Δ Mean central K ≥ 1.5D and ↓ > 5% in mean CCT through 3 consecutive readings/ 6 months | CCL-VARIO, Peschke Meditrade GmbH/ 0.1% riboflavin with 20% dextran solution 30 min | Accelerated: 30mW/cm2 3 min Conventional: 3mW/cm2 30 min |
Cyl and spherical components of refraction improved significantly. No difference observed between the 2 groups. | - | Kmax (conventional): -1.98 ± 0.93 Accelerated: -1.85 ± 0.99 (P = 0.36) |
Conventional: 0.21 ± 0.19 (LogMAR) Accelerated: 0.19 ± 0.20 (LogMAR) (P = 0.64) |
Conventional: 0.17 ± 0.10 (LogMAR) Accelerated: 0.16 ± 0.09 (LogMAR) (P = 0.58) |
Sphere (conventional): From -4.3 ± 1.6 to -2.9 ± 2.0 Sphere (accelerated): -4.8 ± 1.9 to -3.5 ± 2 |
| Tomita et al, 2014 [53] | Prospective comparative study/ Keratoconus | 48; 30 accelerated, 18 conventional | 12 | - | Accelerated: Avedro KXL/ 0.1% riboflavin with HPMC 15 min Conventional: CCL-365 Vario, Peschke Meditrade/ 0.1% riboflavin with 20.0% dextran T500 30 min |
Accelerated: 30mW/cm2 3 min Conventional: 3mW/cm2 30 min |
Both accelerated and conventional CXL were safe and effective. Similar morphologic changes and a pronounced demarcation line were apparent in eyes in both groups postoperatively. | Mean Kmax (accelerated): 50.45 ± 5.28 Mean Kmax (conventional): 48.82 ± 4.56 |
Accelerated: -0.62 ± 1.46 Conventional: -1.77 ± 2.65 (P = 0.21) |
- | - | MRSE (accelerated): 0.64 ± 1.84 MRSE (conventional): 0.39 ± 0.88 (P = 0.60) |
| Kymionis et al, 2014 [54] | Prospective comparative interventional case series/ Keratoconus | 21; 12 accelerated, 9 conventional | 1 | - | CCL-365, Peschke Meditrade/ 0.1% riboflavin with 20% dextran 30 min | Accelerated: 9mW/cm2 10 min Conventional: 3mW/cm2 30 min |
The mean corneal stroma demarcation line depth was 350.78 mum ± 49.34 in the conventional group and 288.46 ± 42.37 mum in the accelerated group. | Mean K steep (conventional): 49.35 ± 2.80 Mean K steep (accelerated): 47.58 ± 2.83 (P = 0.17) |
- | - | - | - |
| Kymionis et al, 2014 [55] | Prospective comparative study/ Keratoconus | 52; 26 accelerated, 26 conventional | 1 | - | CCL-365, Peschke Meditrade/ 0.1% riboflavin with 20% dextran 30 min | Accelerated: 9mW/cm2 14 min Conventional: 3mW/cm2 30 min |
Corneal stromal demarcation line depth showed no significant difference for both groups. | Mean steep K (conventional): 49.88 ± 3.99 Mean steep K (accelerated): 49.17 ± 2.90 (P = 0.467) |
- | - | - | - |
| Mazzotta et al, 2014 [57] | Prospective, comparative, interventional clinical study/ Keratoconus | 20; 10 accelerated pulsed, 10 accelerated continuous | 12 | ↓ UCVA/ BSCVA > 0.50 Snellen lines, ↑ sphere/cyl > 0.50D, ↑ topographic symmetry index SAI/SI > 1D, ↑ mean K > 1D or ↓ thinnest point at corneal OCT pachymetry ≥ 10μm | Avedro KXL/ 0.1% riboflavin dextran-free 10 min | Pulsed: 30mW/cm2 8 min Continuous: 30mW/cm2 4 min |
Better functional outcomes and deeper stromal penetration in pulsed light accelerated treatment. | - | Apical K (Continuous): -1.39 ± 0.38 (P = 0.05) Apical K (Pulsed): +0.15 ± 0.8 (P = 0.077) |
Pulsed: +0.9 ± 1.1 (SDE) (P = 0.10) Continuous: +0.5 ± 1.2 (SDE) (P = 0.65) |
Pulsed: +1.8 ± 1.3 (SDE) (P = 0.55) Continuous: +1.6 ± 1.0 (SDE) (P = 0.56) |
- |
| Woo et al, 2017 [62] | Prospective, non-randomised interventional study | 76; 47 accelerated, 29 conventional | 12 | 1. ↑ ≥ 1D in steepest K 2. ↓ > 5% in minimal corneal thickness 3. ↑ >1D in cyl/ >0.50D SE over ≥ 6 months |
Conventional: UV-X, Peschke Meditrade/ isotonic riboflavin 0.1% with dextran 20% 30 min Accelerated: Avedro KXL/ dextran-free riboflavin 0.1% 10 min |
Conventional: 3mW/cm2 30 min Accelerated: 30mW/cm2 4 min |
Both groups showed no significant increase in K1, K2 and Kmean from baseline at 12 months. No difference between CXL and KXL group for postoperative corneal topography and central and minimal pachymetry/ 12 months. | Steepest K (conventional): 52.29 ± 5.40 Steepest K (accelerated): 52.15 ± 5.30 (P = 0.915) |
Conventional: -0.13 Accelerated: -0.21 (P = 0.829) |
Conventional: -0.11 (LogMAR) (P = 0.017) Accelerated: no statistically significant change |
Conventional: -0.11 (LogMAR) (P = 0.037) Accelerated: -0.08 (P = 0.004) |
SE (conventional): From -4.72 ± 3.6 to -3.82 ± 4.4 (P = 0.247) SE (accelerated): From -4.30 ± 3.1 to -5.11 ± 4.07 (P = 0.131) |