Five‐year results of a prospective, randomised, contralateral eye trial of corneal crosslinking for keratoconus

Abstract

Background Few studies have evaluated corneal crosslinking (CXL) in a prospective, randomised fashion. This study aimed to determine the efficacy and safety of CXL to reduce the progression of keratoconus. Methods Prospective, unmasked, randomised, contralateral eye controlled trial at a tertiary eye centre. Participants: Individuals with bilateral progressive keratoconus. One eye from each subject was randomised to CXL and the contralateral, untreated eye acted as the control. Primary outcome measure: change in maximum keratometry. Secondary outcome measures: uncorrected distance visual acuity, spectacle corrected distance visual acuity, spherical equivalent refraction, simulated keratometry, corneal astigmatism, minimum pachymetry and complications. Results Thirty‐eight individuals (mean age 21.1 ± 6.7 years) were enrolled with one eye treated with CXL. At 5 years, there was a mean decrease in maximum keratometry of treated eyes (−1.45 ± 2.25 D) compared to an increase among the controls (1.71 ± 2.46 D; p < 0.001). There were significant differences between the treated and control groups in the mean change of Steep SimK (−1.07 ± 1.22 vs. 0.96 ± 1.97 D; p < 0.001), Flat SimK (−0.61 ± 1.34 vs. 0.43 ± 1.12 D; p < 0.001), corneal astigmatism (−0.45 ± 1.31 vs. 0.63 ± 1.52 D; p < 0.01) and minimum pachymetry (−32.49 ± 26.32 vs. −13.57 ± 24.11 μm; p < 0.01). Complications included sterile infiltrates (n = 2), microbial keratitis (n = 1), persistent corneal haze/scarring at 5 years (n = 4) and loss of ≥2 lines of corrected distance visual acuity (n = 3). Conclusions CXL is an effective and relatively safe intervention to halt or reduce the progression of keratoconus in the majority of eyes for at least 5 years.

Crosslinking vs. Observation in Fellow Eyes of Keratoconus Patients

“…Currently, epithelium-off CXL is the only FDA-approved treatment that has been reported to slow or halt the progression of KC in its early to moderate stages, with numerous studies supporting its efficacy [ 7 , 8 , 11 ]. A previous study of bilateral sequential CXL versus delayed CXL demonstrated progression in 27% of the patients in the delayed group, and an economical analysis for the office visits saved showed that immediate CXL may be a less costly approach than delayed CXL [ 10 ].…”

“…These results are consistent with a recent study by Meyer et al which assessed the 5-year efficacy of CXL with untreated fellow eyes acting as controls. This study reported that 46% of fellow eye controls that were followed for at least 6 months had progressed in 1D or more and more than 50% remained stable [ 8 ]. Additionally, no statistically significant differences in Kmax or central corneal pachymetry were observed between treatment eyes and naïve fellow eye controls in a 2009 study of KC progression which performed unilateral crosslinking of the worse eye in 19 subjects [ 18 ].…”

Corneal Crosslinking: Present and Future

“…Overall, there were few complications reported. Three studies reported persistent corneal haze lasting up to 60 months 22,25,26. Corneal scars were noted in 3 studies,21,25,26 and there were 2 cases of delayed epithelial healing,20,24 the worst case lasting 9 months 20.…”

“…Three studies reported persistent corneal haze lasting up to 60 months. 22,25,26 Corneal scars were noted in 3 studies, 21,25,26 and there were 2 cases of delayed epithelial healing, 20,24 the worst case lasting 9 months. 20 Two inflammatory responses with infiltrates were treated as microbial keratitis and fully resolved with appropriate treatment, 18,21 and 1 study had permanent scarring from microbial keratitis.…”

Randomised controlled trials in ophthalmology

“…Glancing back over the past 2 years of Clinical and Experimental Ophthalmology reveals a wide range of RCTs with impactful findings. Meyer et al 9 reported 5‐year results of an RCT of Dresden protocol collagen crosslinking in 38 patients with progressive keratoconus, which used the contralateral untreated eye as the control. Allowing for some loss to follow‐up, and interventions to control eyes from 6 months, the investigators could conclude that the procedure stalled disease progression and was relatively safe.…”