Epi-ON corneal crosslinking with UVA for people with Down syndrome and corneal ectasia

Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome

This trial will try Epi-ON corneal crosslinking (riboflavin drops plus UVA light) to see if it can slow or stop corneal thinning and vision loss in people with Down syndrome who have keratoconus or similar ectatic corneal conditions.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 225 (estimated)
• Ages: 8 Years and up
• Sex: All
• Sponsor: Woolfson Eye Institute (Academic / other)
• Locations: 12 sites (Atlanta, Georgia and 11 other locations)
• Trial ID: NCT07135167 on ClinicalTrials.gov

What this trial studies

Participants aged 8 and older with Down syndrome and a diagnosis of keratoconus, pellucid marginal degeneration, forme fruste keratoconus, or other corneal ectasia will receive Epi-ON corneal collagen crosslinking using riboflavin eye drops and UVA exposure. The procedure leaves the corneal epithelium intact (Epi-ON) and is given at specialized Woolfson Eye Institute locations. Subjects will return for up to seven in-office visits over six months for vision and corneal imaging tests to monitor safety and any change in disease progression. The main outcome is whether the treatment slows or halts worsening of corneal shape and vision.

Who should consider this trial

Good fit: Ideal candidates are people aged 8 or older with Down syndrome (or similar cognitive impairment affecting testing) who have a diagnosis of keratoconus or another progressive ectatic corneal condition and can provide consent or have a legally authorized representative consent for them.

Not a fit: Patients without progressive ectatic disease, with severe corneal scarring or unsuitable corneal thickness, or who do not meet the age or consent criteria are unlikely to receive benefit from this procedure.

Why it matters

Potential benefit: If successful, the procedure could slow or stop progression of corneal ectasia and reduce future vision loss, potentially lowering the need for more invasive treatments like corneal transplant.

How similar studies have performed: Conventional epithelium-off corneal crosslinking has demonstrated benefit in slowing keratoconus, while transepithelial (Epi-ON) approaches have shown more mixed results and are less well studied specifically in people with Down syndrome.

Eligibility criteria

Inclusion Criteria:

1. Be at least 8 years of age or older, male or female, of any race.
2. Have a diagnosis of Down syndrome or other cognitive, developmental, or medical conditions that precludes the subject from reliably following instructions or performing some of the study examination procedures.
3. Have a diagnosis of keratoconus, pellucid marginal degeneration, progressive ectasia after previous CXL treatment, other ectatic condition, or forme fruste keratoconus based on topography, tomography, and slit lamp examination.
4. Provide written informed consent and a signed HIPAA form. Pediatric subjects less than 14 years of age must sign an assent, and a parent or legal guardian must sign an informed consent. If the subject has impaired consent capacity, determined by the consenter, the consent form must be signed by the subject's legally authorized representative on behalf of the subject.
5. Satisfactory completion of the standardized clinical decision tool evaluation of patient suitability for CXL. (See Section 7.2.3)
6. Be willing and able to follow all instructions to the best of his/her abilities and comply with the schedule for follow-up visits.

Exclusion Criteria:

1. Normal corneal topography.
2. A history of previous corneal transplant in the study eye.
3. Minimum corneal thickness \< 300 (measured by Pentacam and Ultrasound) at the screening exam.
4. Previous ocular condition (other than refractive error) in the eye(s) to be treated that may predispose the eye to future complications or prevent the possibility of improved vision, for example:

   1. History of, or active, corneal disease (e.g., herpes simplex, herpes zoster keratitis, etc.)
   2. Clinically significant corneal scarring in the central cornea that, in the investigator's opinion, will not allow the subject to achieve functional vision, even with contact lens correction, after the crosslinking procedure.
5. A known contraindication, sensitivity, or allergy to the test article or its components or to study medications.
6. Nystagmus or any other condition that would prevent a steady gaze during the crosslinking treatment or other diagnostic tests.
7. If female, pregnant, lactating or planning a pregnancy, or having a positive urine pregnancy test prior to the randomization of, or treatment of either eye during the course of the study. \[NOTE: If female and capable of becoming pregnant, must agree to use a medically acceptable form of birth control for at least one week prior to the treatment visit and to continue one month following treatment. \]

7\. Inability to remove soft or scleral contact lenses at least 3 days before initial and follow-up examinations.

8\. Inability to remove rigid gas-permeable contact lenses at least 2 weeks before initial and follow-up examinations.

9\. Inability to return for required postoperative examinations. 10. Presence or history or any other condition or finding that, in the investigator's opinion, makes the subject unsuitable as a candidate for crosslinking or study participation or may confound the outcome of the study.

Where this trial is running

Atlanta, Georgia and 11 other locations

• Woolfson Eye Institute — Atlanta, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Atlanta, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Canton, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Cumming, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Douglasville, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Lawrenceville, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Marietta, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Snellville, Georgia, United States (Recruiting)
• Woolfson Eye Institute — Asheville, North Carolina, United States (Recruiting)
• Woolfson Eye Institute — Chattanooga, Tennessee, United States (Recruiting)
• Woolfson Eye Institute — Johnson City, Tennessee, United States (Recruiting)
• Woolfson Eye Institute — Knoxville, Tennessee, United States (Recruiting)

Study contacts

• Study coordinator: LuAnn Bryant

Conditions Down Syndrome; Keratoconus; Pellucid Marginal Degeneration; Forme Fruste Keratoconus; corneal crosslinking; cornea; riboflavin; vitamin B2