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

• Sponsor: Joseph B. Ciolino, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01582880
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 24
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Chemical Injuries; Unspecified Complication of Corneal Transplant; Autoimmune Diseases; Ocular Cicatricial Pemphigoid; Stevens Johnson Syndrome; Lupus Erythematosus, Systemic; Rheumatoid Arthritis; Other Autoimmune Diseases	Drug: Riboflavin	Phase 1/Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Use of Riboflavin/Ultraviolet A Cross-linked Human Donor Corneas as Carriers for the Boston Keratoprosthesis
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Changes in Corneal Thickness at 1 Millimeter [measured at week 4, 6, 26, 32, 52]

   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.

2. Changes in Corneal Thickness at 2 Millimeter [measured at week 4, 6, 26, 32, 52]

   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.

Secondary Outcome Measures

1. Number of Occurrences of Vitritis (Sterile or Infectious) Ulcers [post op week 52]

   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.

2. Ocular Safety [measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52]

   Incidence and severity of ocular adverse events during the study (ophthalmic examination, adverse events spontaneously reported)

3. Systemic Safety [measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52]

   Incidence and severity of systemic adverse events during the study (clinical laboratory, adverse events spontaneously reported).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Joseph B. Ciolino, MD

Investigators

• Principal Investigator: Joseph Ciolino, MD, Massachusetts Eye and Ear Infirmary

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Joseph B. Ciolino, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary
• ClinicalTrials.gov Identifier: NCT01582880
• Other Study ID Numbers: 10-03-020
• First Posted: Apr 23, 2012
• Last Update Posted: Oct 21, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Joseph B. Ciolino, MD, Principal Investigator, Massachusetts Eye and Ear Infirmary: Keratoprosthesis; sterile cornea ulcer
• Additional relevant MeSH terms: Stevens-Johnson Syndrome; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Lupus Erythematosus, Systemic; Autoimmune Diseases; Riboflavin

Study Results

Participant Flow

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	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. Riboflavin: Used to treat donor cornea before implantation
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	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. Riboflavin: Used to treat donor cornea before implantation
Overall Participants	1
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (NA)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%
corneal thickness measured at 1mm one day post op (µm) [Number]
Number [µm]	730
corneal thickness measured at 2mm one day post op (µm) [Number]
Number [µm]	940

Outcome Measures

1. Primary Outcome

Title	Changes in Corneal Thickness at 1 Millimeter
Description	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.
Time Frame	measured at week 4, 6, 26, 32, 52

Outcome Measure Data

Analysis Population Description

52 year old white male patient

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
Measure Participants	1
week 4 corneal thickness	730
week 6 corneal thickness	760
week 26 corneal thickness	700
week 32 corneal thickness	720
week 52 corneal thickness	680

2. Primary Outcome

Title	Changes in Corneal Thickness at 2 Millimeter
Description	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.
Time Frame	measured at week 4, 6, 26, 32, 52

Outcome Measure Data

Analysis Population Description

52 year old white male patient

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
Measure Participants	1
week 4 corneal thickness	940
week 6 corneal thickness	860
week 26 corneal thickness	820
week 32 corneal thickness	795
week 52 corneal thickness	780

3. Secondary Outcome

Title	Number of Occurrences of Vitritis (Sterile or Infectious) Ulcers
Description	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.
Time Frame	post op week 52

Outcome Measure Data

Analysis Population Description

52 year old white male

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
Measure Participants	1
Number [occurrences]	0

4. Secondary Outcome

Title	Ocular Safety
Description	Incidence and severity of ocular adverse events during the study (ophthalmic examination, adverse events spontaneously reported)
Time Frame	measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52

Outcome Measure Data

Analysis Population Description

52 year old white male

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
Measure Participants	1
Number [Incidences]	0

5. Secondary Outcome

Title	Systemic Safety
Description	Incidence and severity of systemic adverse events during the study (clinical laboratory, adverse events spontaneously reported).
Time Frame	measured at day 1, and week 1, 4, 8, 12, 16, 24, 36, 52

Outcome Measure Data

Analysis Population Description

52 year old white male

Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
Measure Participants	1
Number [Incidences]	0

Adverse Events

Time Frame	This study enrolled one study subject. The study subject was followed for Adverse Events from the time of signing the study informed consent form 2/12/2013 to one year post surgery 3/13/2014
Arm/Group Title	Riboflavin Cross-linked Donor Cornea
Arm/Group Description	The donor cornea used as a carrier for the Boston Keratoprosthesis underwent crosslinking treatment before being trephined and prepared for implantation with the Keratoprosthesis. Riboflavin: Used to treat donor cornea before implantation
All Cause Mortality
	Riboflavin Cross-linked Donor Cornea
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Serious Adverse Events
	Riboflavin Cross-linked Donor Cornea
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Riboflavin Cross-linked Donor Cornea
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.