Use of Cross-linked Donor Corneas as Carriers for the Boston Keratoprosthesis

The Use of Riboflavin/Ultraviolet A Cross-linked Human Donor Corneas as Carriers for the Boston Keratoprosthesis

The purpose of the pilot study is to test the efficacy and safety of riboflavin/Ultraviolet A (UVA) cross-linked human donor corneas as carriers for the Boston Keratoprosthesis (Boston KPro) in patients with higher risk for corneal melting (keratolysis).

Study Overview

• Status: Completed
• Conditions: Autoimmune Diseases; Rheumatoid Arthritis; Lupus Erythematosus, Systemic; Ocular Cicatricial Pemphigoid; Stevens Johnson Syndrome; Chemical Injuries; Unspecified Complication of Corneal Transplant; Other Autoimmune Diseases
• Intervention / Treatment: Drug: Riboflavin

Detailed Description

The corneal cross-linking technique has been shown to strengthen the cornea and resist degradation by the body's own enzymes. The use of highly-resistant donor corneas is meant to eliminate the serious post-operative complication of corneal melting (keratolysis) that repeatedly occurs in Boston KPro patients with severe ocular burns, autoimmune and cicatrizing diseases.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts Eye and Ear Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to provide written informed consent and comply with study assessments for the full duration of the study.
2. Age > 18 years.
3. A negative urine pregnancy test.
4. Candidate for a Boston Keratoprosthesis/Corneal transplant.
5. Generally good stable overall health.

6. Patients with an eye at risk for a cornea sterile ulcer which includes:

   • Chemical injuries.
   • Autoimmune diseases (ocular cicatricial pemphigoid, Stevens Johnson Syndrome, systemic lupus erythematosus, rheumatoid arthritis, or other autoimmune diseases).
   • History of previous sterile corneal ulceration requiring a cornea transplant.

Exclusion Criteria:

1. Age < 18 years.
2. Inability to provide written informed consent and comply with study assessments for the full duration of the study.
3. Pregnant or lactating women.
4. No or minimal tear production.
5. Ocular or periocular malignancy.
6. Inability to wear a contact lens due to lid abnormalities or shortened fornix.
7. Signs of current infection, including fever and current treatment with antibiotics.
8. Participation in another simultaneous medical investigation or trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Riboflavin Cross-linked donor cornea; the donor cornea used as a carrier for the Boston Keratoprosthesis will undergo crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis.	Drug: Riboflavin; Used to treat donor cornea before implantation; Other Names: Riboflavin (vitamin B2) 0.1% solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Corneal Thickness at 1 Millimeter	The average carrier graft thickness over the first year of postoperative follow-up. The corneal thickness was measured at each visit using AS-OCT imaging 1 mm away from the KPro stem at 3, 6, 9, and 12 o'clock. The individual corneal thickness measurements (3, 6, 9, and 12 o'clock) where then averaged. The average corneal thickness measurements for week 4, 6, 26, 32 and 52 are reported below.	measured at week 4, 6, 26, 32, 52
Changes in Corneal Thickness at 2 Millimeter	The average carrier graft thickness over the first year of postoperative follow-up. The corneal thickness was measured at each visit using AS-OCT imaging 2 mm away from the KPro stem at 3, 6, 9, and 12 o'clock. The individual corneal thickness measurements (3, 6, 9, and 12 o'clock) where then averaged. The average corneal thickness measurements for week 4, 6, 26, 32 and 52 are reported below.	measured at week 4, 6, 26, 32, 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Occurrences of Vitritis (Sterile or Infectious) Ulcers	Number of occurrence of vitritis (sterile or infectious) ulcers. Incidences of ulcers were collected by way of slit lamp photography from time of surgery to final visit.	post op week 52
Ocular Safety	Incidence and severity of ocular adverse events during the study (ophthalmic examination, adverse events spontaneously reported)	measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52
Systemic Safety	Incidence and severity of systemic adverse events during the study (clinical laboratory, adverse events spontaneously reported).	measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52

Collaborators and Investigators

• Sponsor: Joseph B. Ciolino, MD
• Investigators: Principal Investigator: Joseph Ciolino, MD, Massachusetts Eye and Ear Infirmary

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: April 10, 2012
• First Submitted That Met QC Criteria: April 19, 2012
• First Posted (Estimate): April 23, 2012

Study Record Updates

• Last Update Posted (Actual): October 21, 2019
• Last Update Submitted That Met QC Criteria: October 18, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Keratoprosthesis; sterile cornea ulcer
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Immune System Diseases; Eye Diseases; Connective Tissue Diseases; Stomatognathic Diseases; Mouth Diseases; Hypersensitivity; Erythema; Skin Diseases, Vesiculobullous; Conjunctival Diseases; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Stomatitis; Drug Eruptions; Erythema Multiforme; Drug Hypersensitivity; Lupus Erythematosus, Systemic; Pemphigoid, Bullous; Autoimmune Diseases; Stevens-Johnson Syndrome; Pemphigoid, Benign Mucous Membrane; Physiological Effects of Drugs; Photosensitizing Agents; Dermatologic Agents; Micronutrients; Vitamins; Vitamin B Complex; Riboflavin
• Other Study ID Numbers: 10-03-020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO