Table A4: Safety Studies of Corneal Collagen Cross-Linking*.
| Author, Year | Site, Country | Study Design and Follow-Up | Study Population | Study Objective |
|---|---|---|---|---|
| Bakke E, 2009 (122) | Dpt Ophthalmology, Universities Ulleval, Oslo and Northern Norway | Pre-post consecutive prospective cohort 1 week |
30 P (27 M, 3F) − 30 e Mean age 31.2 yrs± 9.5 (R, 18 to 53) |
To compare the severity of postoperative pain and rate of penetration of riboflavin between eyes treated with CXL and having epithelial removal either mechanically of by excimer laser |
| Goldich Y, 2009 (101) | Dpt Ophthalmology, Assaf Harofeh Medical Center, Tel-Aviv, Israel | Prospective pre-post cohort 6 months |
10 P (7 M, 3 F) − 10 e Mean age 26.5 yrs± 5.7 (R, 18 to 37) |
To assess biomechanical corneal properties, corneal hysteresis (CH) and corneal resistance (CRF) and compensated intraocular pressure (IOP) |
| Greenstein S, 2010 (94) | Cornea and Laser Eye Institute – Hersch Vision Group, CLEI Center for Keratoconus, New Jersey, United States | Prospective RCT − group 1: CXL treated (and fellow untreated eye as control) Group 2: sham riboflavin only 1 year |
44 P (KC 31, post-LASIK ectasia 19) − 50 e and control group 41 e (28 KC, 13 post-LASIK ectasia) | To determine the natural history of CXL associated corneal haze with Scheimpflug 3-D corneal density and slit lamp biomicroscopic analysis |
| Greenstein S, 2011 (100) | United States | Multicenter prospective RCT 1 year |
65 P [54 P (KC), 28 (post LASIK)] − 82 e with untreated fellow-eye as control and sham treated control group 41 e (28KC, 13 post-LASIK ectasia) and fellow untreated eye control 39 e (25 KC, 14 post-LASIK ectasia) | To evaluate the natural course of corneal thickness changes following CXL |
| Grewal D, 2009 (97) | Grewal Eye Institute Chandigarh, India | Pre-post longitudinal comparative cohort 1 year |
102 P (55 M, 47 F) Progressive KC Mean age 25.6 yrs± 4.5 (R, 18 to 31 yrs) |
To evaluate changes in corneal parameters using Scheimpflug imaging post CXL and to examine the effect of UVA exposure on lens density using rotating Scheimpflug imaging and foveal thickness using optical coherence tomography |
| Knappe S, 2011 (104) | Dpt Ophthalmology, University of Rostock, Germany | Prospective pre-post longitudinal cohort | 8 P (6 M, 2 F) − 8 e Progressive KC Mean age 33.6 yrs± 13.9 |
To evaluate the time course of corneal structural changes following CXL using confocal in vivo microscopy |
| Koller T, 2009 (55) | Institute for Refractive and Ophthalmo Surgery, Zurich, Switzerland | Pre-post comparative cohort 1 year |
99 P (62 M, 37F) − 117 e Progressive mild to moderate keratectasia (KC, PMD) | To evaluate failure and complication rates in first postoperative year of CXL |
| Kymionis G, 2009 (90) | Institute of Vision and Optics, University of Crete, Greece | Prospective pre-post comparative cohort 1 year |
10 P − 10 e Progressive KC (n = 5), post-Lasik ectasia (n = 5) Normal (n = 3), Normal post-LASIK (n = 3) |
Compared structural changes using corneal confocal microscopy in post-LASIK ectasia and KC following CXL |
| Kymionis G, 2009 (99) | Institute of Vision and Optics, University of Crete, Greece | Prospective pre-post cohort 1 month |
15 P (10 M, 5 F) − 19 e Mean age 26.9 yrs± 6,5 (R, 17 to 40) |
To evaluate peri-operative pachymetric changes following CXL |
| Kymionis G, 2010 (102) | Institute of Vision and Optics, University of Crete, Greece | Prospective pre-post longitudinal cohort 1 year |
55 P (55 e) Mean age 24.4 yrs±4.1 (R, 18 to 36) | To examine the effect of CXL on intraocular pressure (IOP) by Goldman applanation tonometry (GAT) |
| Lim L, 2011 (95) | Corneal Eye Dpt, Singapore National Eye Center, Singapore | Prospective pre-post cohort 3 month |
30 P (2 case reports both age 23) Progressive KC |
To examine safety and efficacy following CXL and review complications of deep stromal scarring post CXL in mild KC |
| Mazzotta C, 2006 (105) | Dpt Ophthalmological Sciences, Siena University, Italy | Prospective pre-post cohort 6 month |
10 P Progressive KC |
To assess corneal tissue modifications and regeneration of epithelium and sub-epithelial nerve plexus by HRT 11 confocal microscopy following CXL |
| Mazzotta C, 2007 (91) | Dpt Ophthalmology and Neurosurgery, University of Siena, Italy | Prospective pre-post longitudinal cohort study 6 month |
10 P (8 M, 2F) − 10 e Progressive low to moderate KC |
To assess the ultrastructural modifications after CXL with HRT confocal microscopy in patients with progressive KC |
| Mazzotta C, 2007 (96) | Dpt Ophthalmology and Neurosurgery, University of Siena, Italy | Pre-post comparison with untreated fellow-eye as comparison 6 month |
39 P − 40 e Bilateral KC (35 KC in Krumeich stage 1-11, 5 KC in stage 111) |
To review 2 cases of stromal haze during the second and third postop month resistant to topical steroids |
| Mazzotta C, 2008 (92) | Dpt Ophthalmology and Neurosurgery, University of Siena, Italy | Pre-post longitudinal cohort 3 years |
39 P − 44 e | To assess early and late corneal micro-morphological modifications with HRT 11 confocal microscopy following CXL |
| Mencucci R, 2007 (123) | Dpt Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, Italy | Case series Intra-operative | 6 P (3 M, 3 F) − 6 e Bilateral progressive KC |
To assess possible corneal thermal damage during CXL using in vivo surface thermographic analysis |
| Renesto A, 2010 (124) | Vision Institute, Dpt Ophthalmology, Federal University of Sao Paulo, Brazil | Prospective RCT (CXL group vs. riboflavin only) 3 months |
32 P (9 M, 23 F) − 42 e CXL group (19 e): Mean age 29 yrs R, 17 to 55), Control group (22 e): Mean age 31 yrs (R, 22 to 55) |
Cytological examination of ocular surface changes following CXL |
| Sedaghat M, 2010 (103) | Eye Research Center, Mashhad University of Medical Sciences, Iran | Pre-post comparative study 6 months |
51 P (31 M, 20 F) − 56 e | To compare the impact of CXL on 2 corneal biomechanical parameters, corneal hysteresis (CH) and corneal resistance factor (CRF) by waveform analysis |
| Seiler T, 2006 (125) | Institute for Refractive and Ophthalmic Surgery, Zurich, Switzerland | Pre-post comparative cohort 2 weeks |
16 P Progressive KC Mean age 26.4 yrs (R,18 to 39) |
To investigate the CXL induced corneal stromal demarcation line between treated and untreated corneal stroma |
*
E indicates eyes; CXL indicates corneal cross-linking; F indicates female; KC indicates keratoconus; LASIK indicates laser in-situ keratomileusis; M indicates male; Mo indicates month; P indicates patients; PMD indicates pellucid marginal degeneration; Yrs indicates year.