Refractive Corneal Cross-linking for Progressive Keratoconus

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Keratoconus

Intervention / Treatment
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* Procedure: Customised CXL


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Refractive CXL<br>Tomography-customised CXL | Procedure: Customised CXL<br>* 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.<br>* Other names: Riboflavin drops (drug): Vibex Rapid (Avedro Inc.);|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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progressive, cross-linking, customised, refractive