Outcomes of the Sub400 Protocol and Contact Lens-Assisted Corneal Cross-Linking in Advanced Thin-Cornea Keratoconus: Clinical Efficacy and Long-Term Visual Stability.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Outcomes of the Sub400 Protocol and Contact Lens-Assisted Corneal Cross-Linking in Advanced Thin-Cornea Keratoconus: Clinical Efficacy and Long-Term Visual Stability.
Συγγραφείς: Karaca EE; Department of Ophthalmology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey; and., Asfuroğlu Y; Department of Ophthalmology, Ankara Bilkent City Hospital, Ankara, Turkey., Ulusoy DM; Department of Ophthalmology, Ankara Bilkent City Hospital, Ankara, Turkey., Ustael AB; Department of Ophthalmology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey; and., Evren Kemer Ö; Department of Ophthalmology, University of Health Sciences, Ankara Bilkent City Hospital, Ankara, Turkey; and.
Πηγή: Cornea [Cornea] 2026 Oct 01; Vol. 45 (10), pp. 1286-1291. Date of Electronic Publication: 2025 Oct 24.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 8216186 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1536-4798 (Electronic) Linking ISSN: 02773740 NLM ISO Abbreviation: Cornea Subsets: MEDLINE
Imprint Name(s): Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: New York, N.Y. : Masson Pub. USA, c1982-
Ιατρικοί όροι (MeSH): Keratoconus*/drug therapy , Keratoconus*/physiopathology , Keratoconus*/metabolism , Keratoconus*/pathology , Keratoconus*/diagnosis , Corneal Cross-Linking*/methods , Riboflavin*/therapeutic use , Photosensitizing Agents*/therapeutic use , Visual Acuity*/physiology , Cross-Linking Reagents*/therapeutic use , Cornea*/pathology , Photochemotherapy*/methods , Contact Lenses*, Collagen/metabolism ; Corneal Stroma/metabolism ; Humans ; Retrospective Studies ; Female ; Adult ; Male ; Corneal Topography ; Ultraviolet Rays ; Young Adult ; Corneal Pachymetry ; Adolescent ; Treatment Outcome ; Follow-Up Studies
Περίληψη: Purpose: To compare the clinical outcomes of the sub400 protocol and contact lens-assisted corneal cross-linking (CACXL) in patients with keratoconus with corneal thickness below 400 μm.
Methods: This retrospective study included 88 eyes of 88 patients with progressive keratoconus and thinnest pachymetry <400 μm. Group 1 (n = 50) underwent sub400 CXL using individualized fluence at 3 mW/cm2, whereas group 2 (n = 38) received CACXL with 10 mW/cm2 for 9 minutes after functional pachymetry was increased above 400 μm using a riboflavin-soaked contact lens. Outcomes at 12 months included corrected distance visual acuity, keratometric parameters, thinnest corneal thickness, demarcation line (DL) depth, endothelial cell density, and progression rate.
Results: Twelve months after surgery, tomographic stability was maintained in 45 of 50 eyes (90%) in the sub400 CXL group and in 33 of 38 eyes (86.8%) in the CACXL group. No eyes in both groups showed signs of endothelial decompensation. DL depth was significantly greater in the CACXL group (296.32 ± 43.22 μm) than in the sub400 group (266.44 ± 48.63 μm; P = 0.002), with a negative correlation between baseline Kmax and DL depth (ρ = -0.226, P = 0.034). No significant changes were observed in Kmax, Kmean, or postoperative thinnest corneal thickness in both groups (P > 0.05).
Conclusions: Sub400 and CACXL provide similar short-term efficacy and endothelial safety in thin corneas. CACXL achieves deeper stromal penetration, although without superior 12-month visual or topographic outcomes. Longer-term studies are needed to determine whether greater DL depth yields sustained biomechanical or refractive benefits.
(Copyright © 2025 Wolters Kluwer Health, LLC. All rights reserved.)
Competing Interests: The authors have no funding or conflicts of interest to disclose.
References: Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28:293–322.
Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297–319.
Ferraro V, Santoru F, Barone G, et al. Outcomes of iontophoresis cross-linking in asymmetric keratoconus: a retrospective analysis of high visual acuity eyes under 25 years old. Clin Ophthalmol. 2024;18:3399–3403.
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627.
Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66:97–103.
Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet A. I. Principles. Ocul Surf. 2013;11:65–74.
Kamaev P, Friedman MD, Sherr E, et al. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012;53:2360–2367.
Santodomingo-Rubido J, Carracedo G, Suzaki A, et al. Keratoconus: an updated review. Cont Lens Anterior Eye. 2022;45:101559.
Hafezi F, Mrochen M, Iseli HP, et al. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009;35:621–624.
Jacob S, Kumar DA, Agarwal A, et al. Contact lens-assisted collagen cross-linking (CACXL): a new technique for cross-linking thin corneas. J Refract Surg. 2014;30:366–372.
Hafezi F, Kling S, Gilardoni F, et al. Individualized corneal cross-linking with riboflavin and UV-A in ultrathin corneas: the Sub400 protocol. Am J Ophthalmol. 2021;224:133–142.
Belin MW, Kundu G, Shetty N, et al. ABCD: a new classification for keratoconus. Indian J Ophthalmol. 2020;68:2831–2834.
Karaca G, Ocak SY. Investigation of the safety and effectiveness of accelerated contact lens-assisted corneal cross-linking (A-) in thin corneas. Eur J Ophthalmol. 2024;34:1079–1084.
Uysal BS, Ozmen MC, Yuksel M, et al. Comparison of safety and efficacy of silicone hydrogel contact lens-assisted CXL and accelerated CXL in keratoconus patients with thin corneas. Eur J Ophthalmol. 2023;33:44–51.
Malhotra C, Gupta B, Jain AK, et al. Comparison of contact lens-assisted and transepithelial corneal crosslinking with standard epithelium-off crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg. 2022;48:199–207.
Nour MM, El-Agha MSH, Sherif AM, et al. Efficacy and safety of contact lens-assisted corneal crosslinking in the treatment of keratoconus with thin corneas. Eye Contact Lens. 2021;47:500–504.
Karaca EE, Asfuroğlu Y, Ulusoy DM, et al. Evaluating the safety and effectiveness of the sub-400 corneal cross-linking protocol: initial clinical and morphological findings. Int Ophthalmol. 2024;45:16.
Safalı F, Ocak SY, Argon BD, et al. Evaluation of the results of contact lens assisted corneal cross-linking treatment in keratoconus patients with thin corneas. Jpn J Ophthalmol. 2024;68:225–232.
Contributed Indexing: Keywords: Corneal cross linking; corneal ectasia; keratoconus; sub400 protocol
Substance Nomenclature: TLM2976OFR (Riboflavin)
0 (Photosensitizing Agents)
0 (Cross-Linking Reagents)
9007-34-5 (Collagen)
Entry Date(s): Date Created: 20260902 Date Completed: 20260902 Latest Revision: 20260902
Update Code: 20260903
DOI: 10.1097/ICO.0000000000004031
PMID: 42686044
Βάση Δεδομένων: MEDLINE