Corneal Ulcer, Leukoma
Conditions
Brief summary
In this study the safety and effectiveness of biosynthetic cornea, comprising interpenetrating networks of recombinant human collagen and phosphorylcholine, will be tested in patients with severe corneal pathology (corneal ulcers or corneal opacification from corneal injury, burn or infection) - diseases, where human donor cornea transplantation (the only widely accepted treatment) carries a high risk of rejection.
Detailed description
Collagen-phosphorylcholine corneal substitute will be implanted in patient's corneas with severe pathology (corneal ulcer, corneal leukoma after burn, trauma or infection) using anterior lamellar keratoplasty technique, i.e. when patient's diseased cornea is removed it will be substituted with proposed transparent implant. Usually these patients are grafted with human donor cornea, but the latter frequently fails due to graft-versus-host problems. We will test the safety (incidence of adverse events, biocompatability) and the effectiveness (ability to promote healing and increase vision) of developed biosynthetic corneas in 10 patients with corneal pathology, where human donor cornea carries a high risk of rejection. The patients will be follow-uped for 12 months.
Interventions
DEVICECollagen-MPC cornea
Patients will undergo surgery using conventional anterior lamellar keratoplasty technique: diseased cornea will be trephined to approximately 50-90% of corneal thickness (depending on corneal ulcer or scar depth) and then a lamellar dissection will be created. Trephine diameter will depend on ulcer or leukoma maximal size. Alternatively a femtosecond laser may be used to create the dissection. A collagen-phosphorylcholine cornea 250-500 microns thick and equal or 0.25 mm larger diameter is placed and sutured. The sutures are superimposed and the implant and the sutures covered with a bandage contact lens. The sutures and bandage lens will be removed later after the initial healing period of 4 weeks or as determined by physician depending on the implant epithelial coverage.
Sponsors
Linkoeping University
The Filatov Institute of Eye Diseases and Tissue Therapy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must sign and be given a copy of the written Informed Consent form. 2. Subjects with best corrected distance visual acuity 20/200 or worse as a result of corneal ulcer or corneal scar due to burn, injury or infection in the operative eye. 3. Subjects must be willing and able to return for scheduled follow-up examinations for 12 months after surgery.
Exclusion criteria
1. Subjects with severe or life-threatening systemic disease. 2. Subjects with uncontrolled hypertension. 3. Subjects with uncontrolled diabetes or insulin-dependent diabetes. 4. Subjects with glaucoma in either eye. 5. Subjects with marked microphthalmos or aniridia in either eye. 6. Subjects with any other serious ocular pathology, serious ocular complications at the time of corneal transplant underlying serious medical conditions, based on the investigator's medical judgment. 7. Subjects which are or lactating or who plan to become pregnant over the course of the clinical investigation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | 12 months | Implant safety and tolerability will be measured by absence/presence of its lysis as well as by degree of eye inflammation based on conjunctival injection, perifocal corneal haze, aqueous humor transparency, increased intraocular pressure and self reported postoperative pain. Each item is scored 0-4: 0 = no symptom, 4 = severe symptom. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Healed Cornea at 12 Months | 12 months | Cornea is considered to have healed up when there is no defect of corneal epithelium, which is confirmed by fluorescein staining of corneal surface |
| Number of Participants With Improved Visual Acuity at 12 Months | 12 months | Improvement of 1 or more lines in Corrected Distance Visual Acuity in comparison to preoperative visual acuity |
Countries
Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RHCIII-MPC Cornea Substitute Recombinant human collagen type III -methylphosphorylcholine (RHCIII-MPC) cornea substitute transplantation using anterior lamellar keratoplasty technique.
Patients underwent surgery using conventional anterior lamellar keratoplasty technique: diseased cornea was trephined to approximately 50-90% of corneal thickness (depending on corneal ulcer or scar depth) and then a lamellar dissection was created. Trephine diameter depended on ulcer or leukoma maximal size. A RHCIII-MPC cornea 250-500 microns thick and equal or 0.25 mm larger diameter was placed and sutured. The sutures are superimposed and the implant and the sutures covered with a bandage contact lens. The sutures and bandage lens were removed later after the initial healing period of 4 weeks or as determined by physician depending on the implant epithelial coverage. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | RHCIII-MPC Cornea Substitute |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment Ukraine | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Incidence of Treatment-Emergent Adverse Events
Implant safety and tolerability will be measured by absence/presence of its lysis as well as by degree of eye inflammation based on conjunctival injection, perifocal corneal haze, aqueous humor transparency, increased intraocular pressure and self reported postoperative pain. Each item is scored 0-4: 0 = no symptom, 4 = severe symptom.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RHCIII-MPC Cornea Substitute | Incidence of Treatment-Emergent Adverse Events | 0 events |
Secondary
Number of Participants With Healed Cornea at 12 Months
Cornea is considered to have healed up when there is no defect of corneal epithelium, which is confirmed by fluorescein staining of corneal surface
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHCIII-MPC Cornea Substitute | Number of Participants With Healed Cornea at 12 Months | 5 Participants |
Secondary
Number of Participants With Improved Visual Acuity at 12 Months
Improvement of 1 or more lines in Corrected Distance Visual Acuity in comparison to preoperative visual acuity
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RHCIII-MPC Cornea Substitute | Number of Participants With Improved Visual Acuity at 12 Months | 3 Participants |