Clinical trial NCT02514200: Treatment of Keratoconus With Advanced CXL-II
Official title: Treatment of Keratoconus With Advanced Corneal Crosslinking-II
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Keratoconus
Lead sponsor: Umeå University
Sponsor class: OTHER
First posted: 2015-08-03
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether individualized, topography-based corneal crosslinking for keratoconus can improve the optical outcomes of the treatment.

Detailed description: The study is designed as a prospective, open label, randomized controlled trial involving patients aged 12 years or older of both genders with uni- or bilateral keratoconus planned for routine corneal crosslinking (CXL) at the Department of Clinical Sciences / Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study involves 25+25 eyes with keratoconus, which are randomized to receive either conventional pulsed crosslinking with a uniform, universal 8 mm treatment pattern of 5.4 J/cm2 (pCXL; n=25), or a modified treatment - individualized topography-based corneal crosslinking (KXL2; n=25). In the latter treatment zone has an individualized arcuate shape and spares a 2 mm central optical zone. The size of the treatment zone is based on Pentacam HR® corneal tomography, and is determined by the transition zone where the corneal curvature drops off by ≥2D. The energy distribution is based on the maximum corneal steepness (Kmax) value retrieved from the Pentacam HR® tomography: ≤47.0D - 7.2 J/cm2; 47.1-52.0D - 10 J/cm2; ≥52.1D - 15 J/cm2. Thus, the thin protruding areas of the cornea are crosslinked, whereas the parts with a more normal shape are not. The aim is to potentially improve the optical outcome after the treatment.

Patients are randomized to either of the two treatment arms utilizing a computer list of unique random numbers between 1 and 50; an even number will be treated with KXL2 and an uneven number with pCXL. Bilateral inclusion is allowed, and the second eye to be treated will be assigned to the other group, i.e. eye number two will not get the same treatment as eye number 1.

All patients are informed about the procedures and provide oral and written consent before inclusion in the study.

At baseline, before treatment, each eye is evaluated with autorefractometer measurement (Oculus Parc-1®), uncorrected and best spectacle-corrected LogMAR visual acuity, Oculus Pentacam HR® Scheimpflug photography, Oculus CorVis® high-speed Scheimpflug photography, corneal endothelial photography with a specular microscope camera, Goldmann applanation tonometry and biomicroscopy.

For the Pentacam HR® rotating Scheimpflug camera, each eye is photographed using the "25 pictures" program under standardized, mesopic light conditions. Multiple variables will be analyzed, and individual photographs also will be analyzed manually for light backscatter and for the occurrence of a demarcation line, by a masked observer. The corneal biomechanical characteristics are assessed with data from the Oculus CorVis®, and corneal endothelial morphometry, including endothelial cell density is assessed manually and automatically from specular microscopy photographs taken with the Topcon SP-2000 endothelial camera. All investigations are repeated at 1 month, 3 months, 6 months and 12 months after the treatment.

Eligibility criteria: Inclusion Criteria:

1. Patients planned for corneal crosslinking.
2. Uni-or bilateral keratoconus diagnosis based on the Amsler-Krumeich grading and the "Total Deviation" keratoconus quantification value from the "Belin-Ambrosio enhanced ectasia" measurements of the Pentacam HR® Scheimpflug camera, and an altered red reflex and/or an irregular cornea seen as distortion of the keratometric mires.
3. Progression of the keratoconus in the eye in question, documented with Scheimpflug photography using the Oculus Pentacam HR® Scheimpflug camera and/or repeated subjective refraction and keratometry.
4. Minimum corneal thickness of 400 μm at the thinnest point after epithelial removal.
5. ≥12 years of age
6. No ocular abnormalities except keratoconus
7. No previous ocular surgery
8. No cognitive insufficiency interfering with the informed consent.

Exclusion Criteria:

1. Age under 12
2. Any corneal abnormalities except keratoconus
3. Previous ocular surgery
4. Cognitive insufficiency

Primary outcomes:
measure: Change from baseline in refraction
timeFrame: 1, 3, 6 and 12 months after the treatment
Secondary outcomes:
measure: Change from baseline in ETDRS LogMAR visual acuity
timeFrame: 1, 3, 6 and 12 months after the treatment
measure: Change from baseline in corneal densitometry
timeFrame: 1, 3, 6 and 12 months after the treatment
measure: Change from baseline in corneal biomechanical stability measured with GAT
timeFrame: 1, 3, 6 and 12 months after the treatment
measure: Change from baseline in corneal biomechanical stability measured with CorVis®
timeFrame: 1, 3, 6 and 12 months after the treatment
measure: Change from baseline in corneal endothelial morphometry
timeFrame: 1, 3, 6 and 12 months after the treatment
Other outcomes:
Locations:
Study officials:
References:
citation: Nordstrom M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol. 2017 Jul;101(7):920-925. doi: 10.1136/bjophthalmol-2016-309210. Epub 2016 Nov 29.