Corneal Dystrophy, Epithelial Basement Membrane, Corneal Erosions, Epithelial Recurrent Erosion Dystrophy
Conditions
Keywords
Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery
Brief summary
The objective of this clinical study is to test the efficacy of CACICOL20® (RGTA OTR 4120) in improving wound healing and nerve regeneration in the anterior cornea, in a patient population undergoing therapeutic laser treatment for corneal dystrophy or recurrent corneal erosions.
Detailed description
Patients undergoing various surgical treatments of the cornea often suffer from a neural deficit, due to nerves being severed or removed completely during surgery. This can result in pain, impaired epithelial wound healing, reduced tear production, symptoms of dry eye, and loss of ocular surface sensitivity/blink reflex. In addition, surgical wound healing can be accompanied by undesirable formation of scar tissue, which can limit postoperative visual acuity. The investigators' prior clinical experience with patients having undergone surgery of the anterior cornea is that neural recovery is slow and incomplete, while in certain situations scar tissue can form and limit the visual recovery. In this context, CACICOL20®, a regenerative agent approved for use in healing corneal wounds, presents an interesting opportunity for improving postoperative corneal nerve regeneration and a potentially more rapid restoration of the extracellular matrix environment postoperatively, which can lead to improved neural and visual outcomes. The investigators will therefore evaluate the efficacy of CACICOL20® in a randomized, double-blinded clinical study, to evaluate its ability to promote corneal nerve regeneration, epithelial wound healing, and ocular surface recovery postoperatively. Upon inclusion and signing of informed consent, patients undergo preoperative examination. Upon satisfying study criteria, patients are randomized to either treatment or placebo group. Group identity is masked to subjects and to investigators (double-blind). Subjects then undergo therapeutic laser treatment of the cornea in a single clinic, followed by instillation of treatment or placebo in the form of 3 eye drops total (to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery). Postoperative eye examinations are conducted on days 2 and 7 and at month 6 and 12. Examinations include clinical measurement of various eye and corneal wound healing parameters.
Interventions
DEVICECacicol20
Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.
DEVICEPlacebo
Vehicle only in identical packaging, with identical dosage and administration route.
Sponsors
Region Östergötland
Linkoeping University
Sahlgrenska University Hospital
Laboratoires Thea
Neil Lagali
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated informed consent, * Male or female aged ≥ 18 years, * Patient with recurrent erosions or epithelial dystrophies indicated for treatment by phototherapeutic keratectomy of the anterior cornea
Exclusion criteria
* In the affected eye: prior corneal surgery * In either eye: active ocular infection, glaucoma, or ocular hypertension * General history judged by the investigator to be incompatible with the study (life-threatening patient condition). * Known allergic hypersensitivity history to Poly(carboxyMethylGlucoseSulfate) or dextran. * Inability of patient to understand the study procedures and thus inability to give informed consent. * Participation in another clinical study within the last 3 months. * Already included once in this study (can only be included for one treated eye) Specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage recovery in subbasal nerve density. | 12 months postoperative | Degree of corneal subbasal nerve regeneration at one year postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain score on the Visual Analog Scale. | Postoperative day 2, 7, month 6, 12 | Patient self-assessment using the subjective VAS scale (100 point scale). |
| Corneal haze level. | Postoperative month 6, 12 | Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale. |
| Number of postoperative recurrences of erosions. | Postoperative month 12. | As reported by the patient. |
| Percentage recovery in subbasal nerve density. | 6 months postoperative | Degree of corneal subbasal nerve regeneration at 6 months postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy. |
| Percentage of epithelial wound closure. | 2 and 7 days postoperative. | A drop of sodium fluorescein liquid is applied to the cornea, and a digital photograph is taken at high magnification with a clinical slit lamp biomicroscope, using a blue illumination lamp. Area of open wound is measured from photographs and expressed as a percentage of the total treated area. |
| Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry. | Postoperative month 6, 12 | Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry. |
| Sub basal nerve density measured by clinical in vivo confocal microscopy | Postoperative 6 and 12 months | Sub basal nerve density level measured by clinical in vivo confocal microscopy. |
| Epithelial cell density measured by clinical in vivo confocal microscopy | Postoperative 12 months | Epithelial wing cell density measured by clinical in vivo confocal microscopy. |
| Tear production level | Postoperative day 7, month 6, 12 | Tear production level (in mm) measured by the Schirmer test without anesthetic. |
| Tear quality | Postoperative day 7, month 6, 12 | Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking. |
| Improvement in visual acuity | Postoperative day 7, month 6, 12 | Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with adverse events as a measure of safety and tolerability. | From operation day until 12 months postoperative. | Defined as reactions or complications beyond those normally expected after laser corneal surgery. Assessed by the investigator. |
| Number of patients using supplementary eye treatments. | Operation day until 12 months postoperative. | Use of any supplementary eye treatments. |
Countries
Sweden
Outcome results
None listed