Refractive Corneal Cross-linking for Progressive Keratoconus

A Prospective, Controlled Study of Refractive Corneal Cross-linking for Progressive Keratoconus

Young patients with keratoconus face two problems: disease progression and corneal shape irregularity. Both underlie the 20% rate of corneal transplantation in keratoconics required to maintain useful vision.

Corneal collagen cross-linking (CXL) is a now the gold-standard treatment to halt disease progression. The aim is to strengthen the cornea to prevent further shape deterioration. For patients whose quality of vision has already suffered, standard CXL can generally only prevent further deterioration, rather than improving vision. Refractive CXL, a new iteration of CXL in which a bespoke treatment pattern is applied to the cornea, aims to smooth out surface irregularities thereby improving vision.

This primary objective of this study is to compare the visual outcome in patients with progressive keratoconus treated with refractive CXL, as compared with historical controls treated with standard CXL.

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: Customised CXL

Detailed Description

Irregular astigmatism (irregular corneal shape leading to irregular focus) is a common cause of failure to achieve an adequate spectacle correction for many patients with corneal disease. For patients affected, rigid gas permeable contact lenses are the only means of visual rehabilitation. Not all patients tolerate rigid contact lens wear, and those that do are often uncomfortable and have a restricted wearing time.

Keratoconus, in which the corneal shape becomes progressively steeper and more irregular in the 2nd to 4th decades of life, is a common cause of irregular astigmatism. Disease progression in keratoconus can be stabilised with corneal collagen cross-linking (CXL), effective in 90% of cases. Pre-existing irregular astigmatism often remains after CXL, with many patients requiring rigid gas permeable contact lenses to regain good vision.

The investigators have recently demonstrated improvements in vision following simultaneous combined cross-linking with laser refractive surgery (TransPRK/CXL). The excimer laser is used to create a smoother, more regular focusing shape on the cornea to improve the quality of vision achieved in spectacles. Although effective, the downsides of using this approach are both the cost and limited availability of excimer laser equipment in the National Health Service (NHS) in the United Kingdom. Also, excimer laser smoothing works by removing corneal tissue. It is not yet known whether this tissue removal will have any detrimental effect on corneal shape stability post CXL.

As a cheaper and potentially more widely accessible alternative, refractive CXL aims to regularise the corneal surface by applying a bespoke treatment pattern based on pre-operative corneal surface shape (topography) scans. At least two-thirds of patients undergoing standard CXL already have impaired vision at the time treatment. The investigators are aiming to offer these patients both long-term stability of their keratoconus and an improvement in vision in a single treatment.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Moorfields Eye Hospital NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with progressive stage I - III keratoconus
• Corrected distance visual acuity (CDVA) < 0.00 logMAR

Exclusion Criteria:

• Patients under the age of 18 years
• Active ocular surface disease
• Minimum corneal thickness < 375 µm
• Vulnerable groups
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Refractive CXL; Tomography-customised CXL

Procedure: Customised CXL; As for standard CXL, following mechanical removal of the corneal surface layer (epithelium), 0.1% riboflavin drops will be applied every 2 minutes for 10 minutes prior to ultraviolet A (UVA) irradiation - UVA power, distribution and timing as determined by analysis of Pentacam tomography scans. A bandage contact lens will be applied to encourage regrowth of the corneal surface and reduce post-operative pain.; Other Names: Riboflavin drops (drug): Vibex Rapid (Avedro Inc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in corrected distance visual acuity	LogMAR corrected vision in spectacles	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in uncorrected distance visual acuity	LogMAR uncorrected vision without spectacles	24 months
Manifest refraction	Spectacle prescription	24 months
Tomography	Corneal Pentacam indices	24 months
Rates of keratitis	Complications of CXL	24 months

Collaborators and Investigators

• Sponsor: Moorfields Eye Hospital NHS Foundation Trust
• Investigators: Principal Investigator: Daniel M Gore, Moorfields Eye Hospital NHS Foundation Trust

Publications and helpful links

General Publications

• Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye (Lond). 2013 Mar;27(3):329-39. doi: 10.1038/eye.2012.257. Epub 2012 Dec 21.
• O'Brart DP, Chan E, Samaras K, Patel P, Shah SP. A randomised, prospective study to investigate the efficacy of riboflavin/ultraviolet A (370 nm) corneal collagen cross-linkage to halt the progression of keratoconus. Br J Ophthalmol. 2011 Nov;95(11):1519-24. doi: 10.1136/bjo.2010.196493. Epub 2011 Feb 24.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2018
• Primary Completion (Actual): November 27, 2019
• Study Completion (Actual): November 27, 2019

Study Registration Dates

• First Submitted: May 8, 2018
• First Submitted That Met QC Criteria: May 8, 2018
• First Posted (Actual): May 21, 2018

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: cross-linking; progressive; refractive; customised
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: GORD1003

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