Clinical trial NCT03990506: Photorefractive Intrastromal Crosslinking (PiXL) for the Treatment of Progressive Keratoconus
Official title: Comparison of Epi-off and Epi-on Photorefractive Intrastromal Crosslinking (PiXL) for Progressive Keratoconus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Keratoconus
Corneal Crosslinking
Corneal Biomechanics
Corneal Densitometry
Scheimpflug Photography
Corneal Disease
Eye Diseases
Lead sponsor: Umeå University
Sponsor class: OTHER
Collaborators: name: Glaukos Corporation
First posted: 2019-06-19
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, single-masked intraindividually comparing randomized controlled trial. Participants will be randomized to receive Epi-off PiXL in one eye and Epi-on PiXL in the other, which is masked to the participant. The participant can choose to treat in eye at a time or both eyes during the same visit.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety and postoperative ocular discomfort by comparing individually customized Photorefractive intrastromal crosslinking (PiXL) for progressive Keratoconus. The study compares two different protocols, PiXL with corneal epithelium debridement (Epi-off) and PiXL without epithelium debridement in high oxygen environment (Epi-on), with the hypothesis that Epi-on gives less postoperative ocular discomfort.

Detailed description: The study is designed as a prospective, single-masked intraindividually comparing randomized clinical trial involving participants of both genders aged 18-35 years with Keratoconus planned for routine corneal crosslinking at the Department of Ophthalmology, Umeå University Hospital, Umeå, Sweden. The study includes 32 participants with bilateral Keratoconus, receiving Epi-off PiXL (n=32) in one eye and Epi-on PiXL in high oxygen environment (n=32) in the fellow eye. The participants are randomized to epi-on PiXL utilizing block randomization with a sample size of 16 in each block; 16 right eyes and 16 left eyes. All participants are informed about the procedures before consenting to participate in the study.

At baseline, before treatment, each eye is examined with slit-lamp microscopy, subjective refraction, determination of uncorrected (UCVA), low contrast visual acuity at 2.5 percentage contrast and 10 percentage contrast and best corrected (BSCVA) visual acuities using the LogMAR fast protocol and intraocular pressure (IOP) using Goldmann applanation tonometry. Under standardized, mesopic light conditions each eye is evaluated by keratometry readings and central corneal thickness using Schemipflug camera measurements, Pentacam HR® (Oculus, Inc. Lynnwood, WA).

Endothelial cellcount is assessed (SP-2000P, Topcon, Inc) and total ocular wavefront is measured with iTrace (Tracey Technologies, Inc.).

Ocular discomfort is subjectively evaluated in each eye by a specific visual analogous rating scale at 4h, 8h 24h and thereafter daily up to 1 week postoperatively.

All the above mentioned examinations are repeated at 1, 3, 6, 12 and 24 months after treatment. At 1 day and 1 week after treatment, solely UCVA, Auto-refractor measurements and slit-lamp examination are evaluated.

Eligibility criteria: Inclusion Criteria:

* Patients planned for corneal crosslinking.
* Progressive keratoconus documented with a consistent decrease of best corrected visual acuity with no other explanation, an unquestionable historical progression, or a progression documented with the Pentacam Scheimpflug camera with at least 2 of the following: progressive anterior and/or posterior corneal steepening and/or progressive corneal thinning and/or increased rate of corneal thickness change from the periphery to the center.
* A keratoconus diagnosis based on abnormal posterior elevation, abnormal corneal thickness distribution and clinical noninflammatory corneal thinning using the "Belin/Ambrósio enhanced ectasia" measurements of the Pentacam Scheimpflug camera.
* Minimum corneal thickness of 400 µm at the thinnest point before epithelial removal.
* 18-35 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 35
* Any corneal abnormalities except keratoconus
* Pregnancy or lactation
* Previous ocular surgery
* Cognitive insufficiency

Primary outcomes:
measure: Maximal keratometry (Kmax)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Secondary outcomes:
measure: Uncorrected distance visual acuity (UDVA)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Best corrected visual acuity (BCVA)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Mean keratometry (Kmean)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Subjective Ocular Discomfort Scores
timeFrame: 4 hours, 8 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after treatment
measure: Low contrast visual acuity (LCVA)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Manifest spherical equivalent (MRSE)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Central corneal thickness (CCT)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Change from baseline in ocular wavefront aberrometry
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
measure: Endothelial cell density (ECC)
timeFrame: 24 months after treatment
measure: Intraocular pressure (IOP)
timeFrame: 1 month, 3 months, 6 months, 12 months and 24 months after treatment
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: Department of Clinical Sciences/Ophthalmology, Umeå University
Study officials:
affiliation: Department of Clinical Sciences/Ophthalmology, Umeå University
name: Anders Behndig, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: