Transepithelial Accelerated Crosslinking for Progressive Keratoconus: A Critical Analysis of Medium-Term Treatment Outcomes

Abstract

Purpose

To report the 4-year outcomes of transepithelial accelerated corneal collagen crosslinking (TE-ACXL) in the treatment of eyes with progressive keratoconus (KC).

Methods

Eyes of patients who underwent TE-ACXL (6mW/cm² for 15 minutes) for progressive KC and presented 48 months of follow-up were included. Corrected distance visual acuity (CDVA), keratometry measurements (Kmax, maximum keratometry, Kmean, mean keratometry and Astg, corneal astigmatism), thinnest corneal thickness (PachyMin), and topographic, and tomographic indices (specifically the posterior radius of curvature from the 3.0 mm centered on the thinnest point of the cornea (PRC), and the D-index) were analysed preoperatively and every 12 months after TE-ACXL, up to 48 months. Progression after TE-ACXL was considered when eyes presented ≥1 criteria: (1) increase of ≥1D in Kmax or increase of ≥0.75D in Kmean or increase of ≥1D in Astg; (2) reduction of ≥0.085 mm in PRC; (3) decrease ≥5% in PachyMin.

Results

41 eyes from 30 patients were included, with a mean age at crosslinking of 20.90±4.69 years. There was a significant increase in Kmean (+0.64±1.04 D, p<0.001; +0.98 ± 1.49 D, p<0.001; +1.27±2.01 D, p<0.001; +1.13±2.00 D, p=0.006) and a significant decrease in PRC throughout follow-up (−0.12±0.22, p=0.002; −0.15±0.24, p<0.001; −0.17±0.43, p=0.021; −0.16±0.43, p=0.027). PachyMin decreased significantly at 36 and 48 months (−8.50±15.93 μm, p=0.004; −7.82±18.37, p=0.033). According to our progression criteria, there was a major progression rate throughout follow-up (57.1%, 61.1%, 58.8%, and 67.9%, respectively). Surgery and follow-up were uneventful in all subjects. Eleven eyes (26.8%) required further procedures, ≥36 months after the initial TE-ACXL, due to persistent progressive disease.

Conclusion

TE-ACXL proved to be a safe therapeutic option for progressive KC. However, its efficacy is deemed unsatisfactory, as a notable proportion of affected eyes may continue to advance within a 4-year timeframe, necessitating additional procedures to halt the disease’s course.

Keywords:

• progressive keratoconus
• trans-epithelial corneal crosslinking
• epi-on crosslinking
• keratoconus progression

Abbreviations

A-CXL, accelerated corneal collagen crosslinking; CDVA, Corrected distance visual acuity; CXL, Crosslinking; C-CXL, Conventional crosslinking; LogMAR, logarithm of minimal angle of resolution; IHD, Index of height decentration; ISV, Index of surface variance; IVA, Index of vertical asymmetry; K1, Flat Keratometry; K2, Steep Keratometry; KC, Keratoconus classification; Kmax, Maximum keratometry; Km, Mean keratometry; SD, Standard-deviation; TE-ACXL, Transepithelial accelerated corneal collagen crosslinking; TE-CXL, transepithelial corneal collagen crosslinking; UVA, Ultraviolet A.

Data Sharing Statement

Access to any supplemental information such as the study protocol or anonymized data can be available from the Corresponding Author upon reasonable request.

Ethics/Ethical Approval

The study was approved by the Institutional Ethics Review Board of Centro Hospitalar Universitário de São João, Porto, Portugal (certificate approval number CES284/2021). The protocol conformed with the canons of the Declaration of Helsinki for research involving human participants, as well as the European Union’s General Data Protection Regulation. Informed consent was waived in view of the retrospective nature of the study. This article was redacted according to the recommendations of The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.

Acknowledgments

Only the named authors have collaborated in the writing of this paper.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare for this work.

Additional information

Funding

The authors declare that they have no financial ties to this study. No funding or sponsors were undertaken in the preparation of the manuscript.