Abstract
Purpose:
To assess the safety and efficacy of treatment and secondarily determine the topographic changes, visual outcomes, and demarcation line depth after high-fluence pulsed light accelerated cross-linking (ACXL) in pediatric patients (younger than 18 years) with progressive keratoconus.
Methods:
This retrospective analysis included 32 eyes (25 children, aged 11 to 18 years), with progressive keratoconus treated with high-energy epithelium-off pulsed light ACXL (7.2 J/cm2, 15 mW/cm2, 12 minutes, 2 seconds on/1 second off). Corrected distance visual acuity (CDVA), Scheimpflug tomography, and anterior optical coherence tomography measurements were recorded preoperatively and 1, 2, and 3 years postoperatively.
Results:
A total of 32 eyes were included. Significant CDVA improvement, pachymetry, and maximum keratometry reduction were found at all follow-up visits. Mean keratometric values remained stable, and astigmatism showed a mild worsening (< 0.25 D) with statistical significance at 1 and 3 years. Total aberration showed discordant results and coma aberration had a slight improvement without statistical significance. The demarcation line depth was 265 ± 26 μm. Three patients developed mild haze without visual acuity loss. None of the patients underwent a second CXL procedure.
Conclusions:
In pediatric patients, high-fluence epithelium-off pulsed light ACXL appears to be a safe and effective procedure to halt the progression of keratoconus, slightly improving the CDVA and keratometric values.
[J Refract Surg. 2024;40(3):e148–e155.]
- 1. . Management of pediatric keratoconus: evolving role of corneal collagen cross-linking: an update. Indian J Ophthalmol. 2013; 61(8):435–440.
10.4103/0301-4738.116070 PMID:23925333 > Crossref MedlineGoogle Scholar - 2. . Prognostic factors for the progression of keratoconus. Ophthalmology. 1994; 101(3):439–447.
10.1016/S0161-6420(94)31313-3 PMID:8127564 > Crossref MedlineGoogle Scholar - 3. . Keratoconus natural progression: a systematic review and meta-analysis of 11,529 eyes. Ophthalmology. 2019; 126(7):935–945.
10.1016/j.ophtha.2019.02.029 PMID:30858022 > Crossref MedlineGoogle Scholar - 4. . Scalability and severity of keratoconus in children. Am J Ophthalmol. 2012; 154(1):56–62.e1.
10.1016/j.ajo.2012.01.025 PMID:22534107 > Crossref MedlineGoogle Scholar - 5. . [Penetrating keratoplasty in children]. Tunis Med. 2003; 81(7):477–481. PMID:
14534958 > MedlineGoogle Scholar - 6. . Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003; 135(5):620–627.
10.1016/S0002-9394(02)02220-1 PMID:12719068 > Crossref MedlineGoogle Scholar - 7. . Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: a meta-analysis. Invest Ophthalmol Vis Sci. 2018; 59(10):3920–3931.
10.1167/iovs.18-24656 PMID:30073363 > Crossref MedlineGoogle Scholar - 8. . Equivalence of biomechanical changes induced by rapid and standard corneal cross-linking, using riboflavin and ultraviolet radiation. Invest Ophthalmol Vis Sci. 2011; 52(12):9048–9052.
10.1167/iovs.11-7818 PMID:22025568 > Crossref MedlineGoogle Scholar - 9. . Evaluation of corneal changes after conventional versus accelerated corneal cross-linking: a randomized controlled trial. J Refract Surg. 2014; 30(12):837–842.
10.3928/1081597X-20141117-02 PMID:25437483 > LinkGoogle Scholar - 10. . Prospective, randomized contralateral eye study of accelerated and conventional corneal cross-linking in pediatric keratoconus. Int Ophthalmol. 2019; 39(5):971–979.
10.1007/s10792-018-0898-y PMID:29564806 > Crossref MedlineGoogle Scholar - 11. . Comparative efficacy and safety of standard versus accelerated corneal crosslinking for keratoconus: 1-year outcomes from the Save Sight Keratoconus Registry Study. Cornea. 2021; 40(12):1581–1589.
10.1097/ICO.0000000000002747 PMID:33935236 > Crossref MedlineGoogle Scholar - 12. . Efficacy of conventional versus accelerated corneal cross-linking in pediatric keratoconus: two-year outcomes. J Refract Surg. 2020; 36(4):265–269.
10.3928/1081597X-20200302-01 PMID:32267958 > LinkGoogle Scholar - 13. . Corneal cross-linking. Surv Ophthalmol. 2015; 60(6):509–523.
10.1016/j.survophthal.2015.04.002 PMID:25980780 > Crossref MedlineGoogle Scholar - 14. . Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye (Lond). 2014; 28(10):1179–1183.
10.1038/eye.2014.163 PMID:25060847 > Crossref MedlineGoogle Scholar - 15. . Intraobserver reproducibility and interobserver agreement of demarcation line depth measurements following corneal cross linking. Eur J Ophthalmol. 2020; 30(4):635–642.
10.1177/1120672119835116 PMID:30857417 > Crossref MedlineGoogle Scholar - 16. . Standard cross-linking protocol versus accelerated and transepithelial cross-linking protocols for treatment of paediatric keratoconus: a 2-year comparative study. Acta Ophthalmol. 2020; 98(3):e352–e362.
10.1111/aos.14275 PMID:31654497 > Crossref MedlineGoogle Scholar - 17. . Pediatric keratoconus: a review of the literature. Int Ophthalmol. 2018; 38(5):2257–2266.
10.1007/s10792-017-0699-8 PMID:28852910 > Crossref MedlineGoogle Scholar - 18. . Pediatric crosslinking: current protocols and approach. Ophthalmol Ther. 2022; 11(3):983–999.
10.1007/s40123-022-00508-9 PMID:35482230 > Crossref MedlineGoogle Scholar - 19. . Pulsed light accelerated crosslinking versus continuous light accelerated crosslinking: one-year results. J Ophthalmol. 2014; 2014:604731.
10.1155/2014/604731 PMID:25165576 > Crossref MedlineGoogle Scholar - 20. . Stromal demarcation line in pulsed versus continuous light accelerated corneal cross-linking for keratoconus. J Refract Surg. 2016; 32(3):206–208. doi:
10.3928/1081597X-20160204-03 . > LinkGoogle Scholar - 21. . Conventional vs. pulsed-light accelerated corneal collagen cross-linking for the treatment of progressive keratoconus: 12-month results from a prospective study. Exp Ther Med. 2017; 14(5):4238–4244.
10.3892/etm.2017.5031 PMID:29067107 > Crossref MedlineGoogle Scholar - 22. . Comparison of pulsed and continuous accelerated corneal crosslinking for keratoconus: 1-year results at a single center. J Cataract Refract Surg. 2021; 47(5):641–648.
10.1097/j.jcrs.0000000000000488 PMID:33196569 > Crossref MedlineGoogle Scholar - 23. . Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg. 2015; 41(11):2546–2551.
10.1016/j.jcrs.2015.04.033 PMID:26703505 > Crossref MedlineGoogle Scholar - 24. . Comparison of efficacy and safety between standard. accelerated epithelium-off and transepithelial corneal collagen crosslinking in pediatric keratoconus: a meta-analysis. Front Med (Lausanne). 2022; 9:787167. doi:
10.3389/fmed.2022.787167 > Crossref MedlineGoogle Scholar - 25. . Comparison of epithelium-off versus transepithelial corneal collagen cross-linking for keratoconus: a systematic review and meta-analysis. Cornea. 2018; 37(8):1018–1024.
10.1097/ICO.0000000000001632 PMID:29847492 > Crossref MedlineGoogle Scholar - 26. . Analysis of the outcomes of three different cross-linking protocols for treatment of paediatric keratoconus: A multicentre randomized controlled trial. Acta Ophthalmol. 2024; 102(1):e105–e116.
10.1111/aos.15686 PMID:37140143 > Crossref MedlineGoogle Scholar - 27. . Corneal collagen cross-linking with riboflavin and ultraviolet a light for pediatric keratoconus: ten-year results. Cornea. 2018; 37(5):560–566.
10.1097/ICO.0000000000001505 PMID:29319598 > Crossref MedlineGoogle Scholar - 28. . Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents. J Refract Surg. 2012; 28(11):753–758.
10.3928/1081597X-20121011-01 PMID:23347367 > LinkGoogle Scholar - 29. . Two-year corneal cross-linking results in patients younger than 18 years with documented progressive keratoconus. Am J Ophthalmol. 2012; 154(3):520–526.
10.1016/j.ajo.2012.03.020 PMID:22633357 > Crossref MedlineGoogle Scholar - 30. . Accelerated corneal cross-linking in pediatric patients with keratoconus: 24-month outcomes. J Refract Surg. 2014; 30(12):843–849.
10.3928/1081597X-20141120-01 PMID:25437484 > LinkGoogle Scholar - 31. . Accelerated corneal collagen cross-linking in pediatric keratoconus: one year study. Saudi J Ophthalmol. 2017; 31(1):11–18.
10.1016/j.sjopt.2017.01.002 PMID:28337057 > Crossref MedlineGoogle Scholar - 32. . Accelerated corneal crosslinking in children with keratoconus: 5-year results and comparison of 2 protocols. J Cataract Refract Surg. 2020; 46(4):517–523.
10.1097/j.jcrs.0000000000000101 PMID:32271294 > Crossref MedlineGoogle Scholar - 33. . Accelerated corneal collagen cross-linking in pediatric patients: two-year follow-up results. BioMed Res Int. 2014; 2014:894095.
10.1155/2014/894095 PMID:25295278 > Crossref MedlineGoogle Scholar - 34. . Accelerated versus conventional corneal collagen cross-linking in patients with keratoconus: an intra-patient comparative study. Int Ophthalmol. 2018; 38(1):67–74.
10.1007/s10792-016-0423-0 PMID:28035498 > Crossref MedlineGoogle Scholar - 35. . Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results. Cont Lens Anterior Eye. 2018; 41(5):442–447.
10.1016/j.clae.2018.06.001 PMID:29910023 > Crossref MedlineGoogle Scholar - 36. . Transepithelial corneal cross-linking in pediatric patients: early results. J Refract Surg. 2012; 28(11):763–767.
10.3928/1081597X-20121011-03 PMID:23347369 > LinkGoogle Scholar - 37. . Accelerated epi-on versus standard epi-off corneal collagen cross-linking for progressive keratoconus in pediatric patients: five years of follow-up. Cornea. 2020; 39(12):1493–1498.
10.1097/ICO.0000000000002463 PMID:32796273 > Crossref MedlineGoogle Scholar - 38. . Efficacy of epithelium-off and epithelium-on corneal collagen cross-linking in pediatric keratoconus. Eye Contact Lens. 2017; 43(3):155–161.
10.1097/ICL.0000000000000255 PMID:26925536 > Crossref MedlineGoogle Scholar - 39. . Central corneal thickness after cross-linking using high-definition optical coherence tomography, ultrasound, and dual scheimpflug tomography: a comparative study over one year. Am J Ophthalmol. 2016; 167:38–47.
10.1016/j.ajo.2016.04.004 PMID:27084001 > Crossref MedlineGoogle Scholar - 40. . Long-term visual, refractive and topographic outcomes of “epioff” corneal collagen cross-linking in pediatric keratoconus: standard versus accelerated protocol. Clin Ophthalmol. 2020; 14:3747–3754.
10.2147/OPTH.S275797 PMID:33177802 > Crossref MedlineGoogle Scholar - 41. . Analysis of total corneal astigmatism with a rotating Scheimpflug camera in keratoconus. BMC Ophthalmol. 2020; 20(1):475.
10.1186/s12886-020-01747-9 PMID:33272234 > Crossref MedlineGoogle Scholar - 42. . Comparison of anterior, posterior, and total corneal astigmatism measured using a single Scheimpflug camera in healthy and keratoconus eyes. Korean J Ophthalmol. 2018; 32(3):163–171.
10.3341/kjo.2017.0075 PMID:29770640 > Crossref MedlineGoogle Scholar - 43. . Repeatability of Scheimpflug based corneal tomography parameters in advanced keratoconus with thin corneas. Eye (Lond). 2023; 37(16):3429–3434.
10.1038/s41433-023-02528-6 PMID:37076688 > Crossref MedlineGoogle Scholar - 44. . Stromal demarcation line in pulsed versus continuous light accelerated corneal cross-linking for keratoconus. J Refract Surg. 2016; 32(3):206–208.
10.3928/1081597X-20160204-03 PMID:27027629 > LinkGoogle Scholar - 45. . Accelerated corneal crosslinking for treatment of keratoconus in children and adolescents under 18 years of age. Klin Monbl Augenheilkd. 2023; 240(10):1131–1142.
10.1055/a-1933-3084 PMID:36436508 > Crossref MedlineGoogle Scholar - 46. . Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Invest Ophthalmol Vis Sci. 2014; 55(5):2881–2884.
10.1167/iovs.13-13748 PMID:24677109 > Crossref MedlineGoogle Scholar - 47. . Changes in corneal biomechanical properties with different corneal cross-linking irradiances. J Refract Surg. 2018; 34(1):51–58.
10.3928/1081597X-20171025-01 PMID:29315442 > LinkGoogle Scholar - 48. . Pachymetry-based accelerated crosslinking: the “M nomogram” for standardized treatment of all-thickness progressive ectatic corneas. Int J Keratoconus Ectatic Corneal Dis. 2018; 7(2):137–144.
10.5005/jp-journals-10025-1171 > CrossrefGoogle Scholar - 49. . Oxygen kinetics during corneal cross-linking with and without supplementary oxygen. Am J Ophthalmol. 2021; 223:368–376.
10.1016/j.ajo.2020.11.001 PMID:33227242 > Crossref MedlineGoogle Scholar - 50. . A proposed concentration-controlled new protocol for optimal corneal crosslinking efficacy in the anterior stroma. Invest Ophthalmol Vis Sci. 2018; 59(1):431–432.
10.1167/iovs.17-23414 PMID:29365149 > Crossref MedlineGoogle Scholar - 51. . Comparative functional outcomes after corneal crosslinking using standard, accelerated, and accelerated with higher total fluence protocols. Cornea. 2019; 38(4):433–441.
10.1097/ICO.0000000000001878 PMID:30681515 > Crossref MedlineGoogle Scholar - 52. . Comparison between pulsed and continuous accelerated corneal cross-linking protocols. Clin Ophthalmol. 2023; 17:1407–1413.
10.2147/OPTH.S409178 PMID:37214154 > Crossref MedlineGoogle Scholar - 53. . Independent-effect comparison of five crosslinking procedures for progressive keratoconus based on keratometry and the ABCD Grading System using generalized estimating equations (GEE). BMC Ophthalmol. 2023; 23(1):16.
10.1186/s12886-022-02744-w PMID:36627585 > Crossref MedlineGoogle Scholar - 54. . High-fluence accelerated epithelium-off corneal cross-linking protocol provides Dresden protocol-like corneal strengthening. Transl Vis Sci Technol. 2021; 10(5):10.
10.1167/tvst.10.5.10 PMID:34542574 > Crossref MedlineGoogle Scholar - 55. . Analysis of biomechanical response after corneal crosslinking with different fluence levels in porcine corneas. Curr Eye Res. 2023; 48(8):719–723.
10.1080/02713683.2023.2205612 PMID:37144469 > Crossref MedlineGoogle Scholar