A Randomized Clinical Trial of Ex Vivo Corneal Cross-Linking of Donor Keratoplasty Tissue for Keratoconus Used for Keratoplasty in Keratoconus Patients

NCT04584125 | Not Yet Recruiting DMC

• 1 other identifier: 2020P002132
• Study Type: interventional
• Target: 216
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized clinical trial will assess corneal astigmatism and visual outcomes in participants who have undergone corneal transplantation for keratoconus with ex vivo cross-linked donor corneal tissue versus participants who have undergone corneal transplantation for keratoconus with non-cross-linked donor corneas. Crosslinking is a procedure that stabilizes the biomechanical properties of the cornea; as a result, the cornea stiffens. It has been shown that this procedure stabilizes the cornea of patients with keratoconus or corneal ectasias. The FDA currently approves crosslinking for patients with progressive keratoconus and corneal ectasia following refractive surgery. Ex vivo crosslinking of donor corneal tissue for patients with keratoconus undergoing PK or DALK could stabilize the cornea and reduce the risk of high astigmatism and improve vision in patient with keratoconus.

Conditions

Keratoconus

Keywords

Corneal Crosslinking; Penetrating Keratoplasty; Deep Anterior Lamellar Keratoplasty

Outcome Measures

Primary Outcomes (1)

• • Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery.

  • Keratometric astigmatism with Pentacam Schiempflug imaging at 130 weeks post-surgery

  130 weeks

Secondary Outcomes (4)

• • Best spectacle corrected visual acuity (BSCVA) with ETDRS methodology at 2.5 years (130 weeks) post-surgery

  130 weeks

• Manifest cylinder astigmatism at 130 weeks post-surgery

  130 weeks

• Uncorrected visual acuity (UCVA) 130 weeks post-surgery

  130 weeks

• Low-contrast BSCVA with ETDRS methodology at 130 weeks post-surgery

  130 weeks

Study Arms (2)

Ex vivo cross linking of donor corneal tissue

EXPERIMENTAL

Treatment Arm: The donor corneal tissue used in the PK or DALK procedures will previously undergo ex vivo crosslinking.

Drug: Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light

Non-cross-linked donor corneal tissue for keratoplasty

SHAM COMPARATOR

Control Arm: The donor corneal tissue used in the PK or DALK procedures will not previously undergo ex vivo crosslinking.

Drug: Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light

Interventions

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% without UV light DRUG

The corneal tissue for the control arm will be treated the same as the crosslinked tissue except that it will not be exposed to ultraviolet light. The donor cornea will be placed on an artificial anterior chamber maintainer and the epithelium will be removed mechanically. Riboflavin solution (0.1% riboflavin and 20% dextran supplied in a sterile, single-dose container) will be applied to the cornea every 2 minutes for 30 minutes.

Also known as: PHOTREXA VISCOUS

Non-cross-linked donor corneal tissue for keratoplasty

Riboflavin 5'-phosphate in 20% dextran ophthalmic solution) 0.146% with UV light DRUG

A wavelength of 365 nm ultraviolet A light will be used to direct 5.4 J/cm2 using a beam diameter of 9.5mm to treat the de-epithelialized corneal surface of a donor cornea for 30 minutes. Every 2 minutes, the UV light will be used while another drop of riboflavin is applied on top of the donor cornea.

Also known as: PHOTREXA VISCOUS

Ex vivo cross linking of donor corneal tissue

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide written informed consent.
• Willing and able to comply with study assessments for the full duration of the study.
• Age ≥18 years but ≤50 years
• History of keratoconus (without a previous transplant) requiring keratoplasty
• Willing to commit to not having further cross-linking, corneal relaxing incisions, intacs, or corneal laser vision correction during the course of the study

You may not qualify if:

• Age \< 18 years \>50
• Inability to provide written informed consent and comply with study assessments for the full duration of the study
• Participation in another simultaneous interventional medical investigation or trial
• Systemic
• History of Stevens-Johnson syndrome or ocular pemphigoid
• Signs of current infection, including fever and current treatment with antibiotics
• Pregnancy (positive pregnancy test) or lactating
• Pre-menopausal sexually active women not using adequate contraception (Reliable intrauterine devices, hormonal contraception or a spermicide in combination with a barrier method)
• Recipient Eye
• Corneal or ocular surface infection within 30 days prior to study entry
• History of previous cross-linking
• History of previous corneal transplant
• Non-healing epithelial defect of at least 0.5x0.5 mm in host corneal bed lasting ≥6 weeks preoperatively
• Ocular or periocular malignancy
• Lid abnormalities that in the opinion of the investigator could confound the study results and these include clinically significant ectropion, lagophthalmos, cicatrization, entropion, and rosacea

Sponsors & Collaborators

• Joseph B. Ciolino, MD: lead

Study Sites (1)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Related Publications (26)

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MeSH Terms

Conditions

Keratoconus

Interventions

Flavin Mononucleotide; Ultraviolet Rays

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Riboflavin; Flavins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring; Coenzymes; Enzymes and Coenzymes; Ribonucleotides; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Pigments, Biological; Biological Factors; Light; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Optical Phenomena; Radiation; Radiation, Ionizing; Radiation, Nonionizing; Sunlight; Weather; Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Officials

• Joseph B Ciolino

  Massachusetts Eye and Ear

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph B Ciolino, MD

CONTACT

(617) 573-3938; Joseph_Ciolino@MEEI.HARVARD.EDU

Ellen Fitzgerald

CONTACT

617-573-6971; Ellen_Fitzgerald@MEEI.HARVARD.EDU

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Ophthalmology

Model Details: The study is a multicenter, double-masked, parallel, and randomized study with a subsequent follow-up period of 30 months. 216 subjects (of any race or gender) who have keratoconus (between the ages of 18 and 50) will sign the consent for their first PK or DALK surgery in the study eye. Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be given the opportunity to participate in the study. Subjects will either randomized to the treatment group (crosslinked corneal tissue) or control group (non-crosslinked corneal tissue that has been exposed to riboflavin, but no ultraviolet light).

Study Record Dates

• First Submitted: October 5, 2020
• First Posted: October 12, 2020
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)