Accelerated and Standard Corneal Cross-Linking Protocols in Patients with Down Syndrome: A Non-inferiority Contralateral Randomized Trial

Abstract

Introduction To compare the results of an accelerated corneal cross-linking (CXL) protocol (9 mW/cm 2 , 10 min) with the standard CXL protocol (3 mW/cm 2 , 30 min) in patients with Down syndrome (DS) who have keratoconus (KC). Methods Twenty-seven 10- to 20-year-old patients with DS who had bilateral progressive KC were enrolled in a contralateral randomized trial and completed 2 years of follow-up examinations. Fellow eyes were randomly allocated to the accelerated CXL group or the standard CXL group. The main outcome measure was change in maximum keratometry (K max ) centered on the steepest point (zonal K max − 3 mm) with a non-inferiority margin of 1.0 diopter (D). Vision and refraction tests, ophthalmic examinations, and corneal tomography were performed at baseline and at 6, 12, and 24 months after CXL. Failure was defined as an increase of ≥ 1.0 D in zonal K max − 3 mm within a 12-month period. Results The mean age (± standard deviation) of the patients was 15.71 ± 2.40 years. The within-group change in zonal K max − 3 mm was not significant after 2 years in either group, and within-group zonal K max − 3 mm remained stable. At 2 years after CXL, the mean change in the zonal K max − 3 mm was – 0.02 ± 0.81 D and – 0.31 ± 0.86 D in the accelerated CXL and standard CXL groups, respectively ( P = 0.088). At 1 year of follow-up, three patients in the accelerated CXL group showed treatment failure (mean change in zonal K max − 3 mm + 2.12 ± 0.11 D); no patients in the standard CXL group showed treatment failure. At 2 years of follow-up, these three patients showed a decrease of – 0.43 ± 0.18 D in zonal K max − 3 mm from a baseline value of 55.11 ± 0.32 D. The 2-year trends of the inferior–superior asymmetry and vertical coma were statistically significantly different between the two groups, with the accelerated CXL protocol showing superiority in patients with higher baseline values. Conclusion In young patients with Down syndrome, the accelerated CXL protocol was able to halt disease progression and may be an alternative for the standard CXL protocol. In advanced KC, the efficacy of the accelerated approach was delayed and appeared later in the follow-up. In asymmetric cornea, the accelerated CXL resulted in centralization of the corneal cone. Trial Registration Iranian Registry of Clinical Trials, IRCT20100706004333N3 Electronic supplementary material The online version of this article (10.1007/s40123-020-00303-4) contains supplementary material, which is available to authorized users.

Keratoconus in Down syndrome: Prevalence, risk factors, severity and corneal tomographic characteristics

“…Although corneal haze and sterile infiltrates have been associated with DS, 25 it has been shown that keratoconus can be effectively managed with epithelium-off accelerated CXL in DS. 26 This study identified a high prevalence of ACH (14%) in people with DS affected with keratoconus, while ACH is estimated to affect approximately 3% of the general population with keratoconus. 24,27,28 ACH is a painful and potentially blinding stage of keratoconus and may result in the need for corneal transplantation which is a costly procedure with significant associated risks.…”

Management of Keratoconus in Down Syndrome and Other Intellectual Disability

“…All treated patients had accelerated protocol epithelium-off CXL comprising 8-mm alcohol-assisted epithelial debridement and isotonic riboflavin 0.1% saturation (Vibex Rapid; Medio-Haus-Medizinprodukte GmbH, Kiel, Germany) for 10 minutes and 4 minutes of ultraviolet A irradiation with a total energy of 30 J/m 2 shown to be comparable with the Dresden protocol for nonadvanced KC. 22,23 After the procedure, all patients were treated with topical steroid (prednisolone acetate 1% QID; Allergan plc) for 2 weeks and topical antibiotic prophylaxis (chloramphenicol 0.5% QID) until reepithelialization. Patients were reviewed at 1 week for removal of bandage contact lens, then 1 month and 6 months.…”

Corneal Crosslinking: Present and Future

“…Hashemi et al 53 completed an RCT of conventional CXL versus ACXL in subjects with Trisomy 21. The group studied 27 subjects under 20 years of age and showed that both conventional CXL and ACXL procedures effectively halted disease progression.…”