Epithelium-on Cross-linking Versus Observation of Fellow Eyes of Patients With Unilateral Clinically Evident Keratoconus

Epithelium-on Accelerated Corneal Cross-linking Versus Observation of Fellow Eyes of Young Patients With Unilateral Clinically Evident Keratoconus

Keratoconus (KC) is a bilateral asymmetric progressive corneal degenerative disease. The management of young patients, diagnosed with clinically evident KC in one eye and with no clinical signs of KC in the other eye, represents a real challenge for many ophthalmologists.

The aim of the current study is to investigate the effectiveness and safety of epithelium-on accelerated CXL to stabilize the eye with no clinical signs of KC, in young patients with unilateral clinically evident KC, compared with standard care and follow-up only.

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: Epithelium-on corneal cross-linking (epi-on CXL)

Detailed Description

Keratoconus (KC) is a bilateral asymmetric progressive corneal degenerative disease associated with corneal thinning and protrusion with resultant irregular astigmatism and visual loss.

Although several studies showed that epithelium-off corneal cross-linking (epi-off CXL) is more effective in preventing KC progression compared with epithelium-on corneal cross-linking (epi-on CXL), the removal of corneal epithelium in epi-off CXL might be associated with a number of serious complications such as persistent epithelial defects and sight-threatening infectious keratitis. Additionally, recent systematic reviews and meta-analysis concluded that epi-on CXL is as effective as epi-off CXL in terms of visual and topographic stability of keratoconus, but has the advantage of being much safer avoiding the complications of epithelial removal.

The management of the better eye, of young patients with unilateral clinically evident KC, is controversial. Some ophthalmologists prefer to cross-link the better eye, while others prefer to conservatively follow it up, in order to avoid complications of epithelial removal in epi-off CXL.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71516
    • TIBA Eye Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

This retrospective comparative study was conducted at a refractive and corneal surgery center in Assiut (Private practice). The study included young patients who were diagnosed with forme fruste or subclinical keratoconus.

Description

Inclusion Criteria:

Patients aged 12 to 30 years presented with forme fruste (FFKC) or subclinical KC, based on the following criteria:

1. Normal slit lamp examination
2. Normal topography in FFKC and suspicious topography in subclinical KC with asymmetric bow-tie or inferior steeping (inferior-superior value less than 1.40 D in the anterior sagittal curvature map in pentacam)
3. Clinical and topographic features of KC in the other eye.

Exclusion Criteria:

1. Corrected distance visual acuity (CDVA) worse than 0.1 logMAR
2. Corneal thickness at the thinnest location less than 400 μm
3. Severe ocular allergy (active catarrhal keratoconjunctivitis)
4. Other corneal or ocular diseases
5. Systemic diseases such as diabetes mellitus and autoimmune diseases

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Epithelium-on corneal cross-linking group; Patients in this group underwent epithelium-on accelerated corneal cross-linking (epi-on CXL) for the eye with no clinical signs of keratoconus.	Procedure: Epithelium-on corneal cross-linking (epi-on CXL); In epithelium-on corneal cross-linking (epi-on CXL), the cornea is soaked with riboflavin for 10 minutes (Paracel® for 4 minutes and VibeX-xtra® for 6 minutes) . Thereafter, the cornea is subjected to ultraviolet A at a wavelength of 370 nm to give a total dose of 5.4 J/cm² through 10 milliwatt mW/cm² for 9 minutes.
Follow-up group; Patients in this group were planned to have regular follow-up visits, without intervention, for the eye with no clinical signs of keratoconus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steep keratometry value	The steep keratometry is measured using pentacam. A higher value means a worse outcome.	24 months
Maximum keratometry value	The maximum keratometry is measured using pentacam. A higher value means a worse outcome.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corrected distance visual acuity	Corrected distance visual acuity (CDVA) is measured with Snellen's acuity chart and converted to logarithm of the minimum angle of resolution (logMAR) notation. The higher the logMAR CDVA, the worse the outcome.	24 months

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: Mahmoud Abdel-Radi, MD, Assiut University

Publications and helpful links

General Publications

• Koh S, Inoue R, Maeda N, Kabata D, Shintani A, Jhanji V, Klyce SD, Maruyama K, Nishida K. Long-term Chronological Changes in Very Asymmetric Keratoconus. Cornea. 2019 May;38(5):605-611. doi: 10.1097/ICO.0000000000001890.
• Henriquez MA, Hadid M, Izquierdo L Jr. A Systematic Review of Subclinical Keratoconus and Forme Fruste Keratoconus. J Refract Surg. 2020 Apr 1;36(4):270-279. doi: 10.3928/1081597X-20200212-03.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): January 31, 2024
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: February 12, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Keratoconus; Corneal cross-linking; Epithelium-on CXL
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: EOCXLFE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No