Treatment of Keratoconus With Advanced Corneal Crosslinking

The purpose of this study was to determine whether mechanical compression of the cornea during corneal crosslinking for keratoconus using a sutured rigid contact lens can improve the optical outcomes of the treatment.

Study Overview

• Status: Completed
• Conditions: Keratoconus
• Intervention / Treatment: Procedure: Corneal reshaping/crosslinking (CRXL); Procedure: Corneal Crosslinking (CXL)

Detailed Description

The study is designed as a prospective, open, randomized controlled trial involving patients aged 18-28 years of both genders with uni- or bilateral keratoconus planned for routine corneal crosslinking at the Department of Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study involves 30+30 eyes with keratoconus, which are randomized to receive either conventional corneal crosslinking (n=30) using the Dresden protocol or a modified treatment - corneal reshaping and crosslinking (n=30), where a rigid contact lens is sutured to the cornea during the treatment to flatten the corneal curvature and potentially improve the optical outcome after the treatment. Patients are randomized utilizing a list of unique random numbers between 1 and 60. All patients are informed about the procedures before consenting to participate in the study. The study also involves 60 eyes of healthy age- and sex-matched control subjects.

At baseline, before treatment, each eye is evaluated with autorefractometer measurement, best spectacle-corrected LogMAR visual acuity, Pentacam Scheimpflug photography, Goldmann applanation tonometry and biomicroscopy. The corneal biomechanical characteristics are assessed with applanation resonance tonometry and the ocular response analyzer. The investigations are repeated at 1 month, 6 months, 2 years and 5 years after the treatment.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 28 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients planned for corneal crosslinking.
• Progressive keratoconus documented with Scheimpflug photography using the Pentacam Scheimflug camera and/or repeated subjective refraction and keratometry.
• A keratoconus diagnosis based on the Amsler-Krumeich grading and the "Total Deviation" KC quantification value from the "Belin-Ambrosio enhanced ectasia" measurements of the Pentacam Scheimpflug camera, and an altered red reflex and/or an irregular cornea seen as distortion of the keratometric mires.
• Minimum corneal thickness of 400 µm at the thinnest point after epithelial removal.
• 18-28 years of age
• No ocular abnormalities except keratoconus
• No previous ocular surgery
• No cognitive insufficiency interfering with the informed consent.

Exclusion Criteria:

• Age under 18 or over 28
• Any corneal abnormalities except keratoconus
• Previous ocular surgery
• Cognitive insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Corneal reshaping/crosslinking (CRXL); Corneal crosslinking with compression of the cornea using a sutured rigid contact lens during the treatment.	Procedure: Corneal reshaping/crosslinking (CRXL); The keratoconus cornea is treated with epithelial debridement in local anesthesia, is soaked in Riboflavin by repeated topical application during 30 minutes. A flat, rigid contact lens is sutured to the cornea and the cornea and is then irradiated with ultraviolet light 5.4 J/cm2 during 30 minutes.
ACTIVE_COMPARATOR: Corneal crosslinking (CXL); Standard corneal crosslinking using the Dresden protocol.	Procedure: Corneal Crosslinking (CXL); The keratoconus cornea is treated with epithelial debridement in local anesthesia, is soaked in Riboflavin by repeated topical application during 30 minutes. The cornea and is then irradiated with ultraviolet light 5.4 J/cm2 during 30 minutes.
NO_INTERVENTION: Control group to CRXL; Healthy subjects, age- and sex-matched to the CRXL group.
NO_INTERVENTION: Control group to CXL; Healthy subjects, age- and sex-matched to the CXL group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in refraction	Refractive errors, including lower and higher order aberrations in the cornea	1, 6, 24 and 60 months after the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in ETDRS LogMAR visual acuity	Uncorrected and best spectacle corrected visual acuity measured with the Early treatment diabetic retinopathy study, graded in logarithmic values of the minimal angle of resolution	1, 6, 24 and 60 months after the treatment
Change from baseline in corneal biomechanical stability measured with ORA	Biomechanical stability assessed with the ocular response analyzer	1, 6, 24 and 60 months after the treatment
Change from baseline in corneal biomechanical stability measured with ART	Biomechanical stability assessed with the applanation resonance tonometer	1, 6, 24 and 60 months after the treatment
Change from baseline in corneal biomechanical stability measured with GAT	Biomechanical stability assessed with the Goldmann applanation tonometer	1, 6, 24 and 60 months after the treatment
Change from baseline in corneal densitometry	Corneal light reflectivity (back scatter) assessed with the Pentacam HR Scheimpflug camera	1, 6, 24 and 60 months after the treatment

Collaborators and Investigators

• Sponsor: Umeå University
• Investigators: Principal Investigator: Anders Behndig, Professor, Umeå University

Publications and helpful links

General Publications

• Beckman Rehnman J, Behndig A, Hallberg P, Linden C. Initial results from mechanical compression of the cornea during crosslinking for keratoconus. Acta Ophthalmol. 2014 Nov;92(7):644-9. doi: 10.1111/aos.12380. Epub 2014 Mar 15.
• Beckman Rehnman J, Behndig A, Hallberg P, Linden C. Increased corneal hysteresis after corneal collagen crosslinking: a study based on applanation resonance technology. JAMA Ophthalmol. 2014 Dec;132(12):1426-32. doi: 10.1001/jamaophthalmol.2014.3029.
• Beckman Rehnman J, Janbaz CC, Behndig A, Linden C. Spatial distribution of corneal light scattering after corneal collagen crosslinking. J Cataract Refract Surg. 2011 Nov;37(11):1939-44. doi: 10.1016/j.jcrs.2011.05.028. Epub 2011 Aug 27.
• Rehnman JB, Linden C, Hallberg P, Behndig A. Treatment Effect and Corneal Light Scattering With 2 Corneal Cross-linking Protocols: A Randomized Clinical Trial. JAMA Ophthalmol. 2015 Nov;133(11):1254-60. doi: 10.1001/jamaophthalmol.2015.2852.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: April 13, 2015
• First Submitted That Met QC Criteria: April 20, 2015
• First Posted (ESTIMATE): April 23, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 9, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Keratoconus; Corneal biomechanics; Corneal crosslinking; Corneal densitometry; Scheimpflug photography
• Additional Relevant MeSH Terms: Eye Diseases; Corneal Diseases; Keratoconus
• Other Study ID Numbers: CRXL