Facilitation of Corneal Re-epithelialization After Photorefractive Keratectomy
Study Details
Study Description
Brief Summary
Photorefractive keratectomy (PRK) or surface ablation is one of the most commonly used surgical procedures to correct refractive errors, which was proved to be safe and effective. In PRK, the corneal epithelium is removed by various techniques such as diluted alcohol, manual debridement, brush, or excimer laser, before the refractive excimer laser ablation of the corneal stroma. Compared to laser in situ keratomileusis (LASIK), the two main drawbacks for PRK are slower visual recovery and discomfort in the immediate postoperative period, due to the epithelial removal.
Corneal healing is a complex process involving cellular interaction and reaction with various molecules (proteases, growth factors, and epithelial and stromal cytokines). Enhanced corneal re-epithelialization may reduce the risk for corneal infection and stromal scarring or melting. Over the past few years, a new type of matrix therapy by ReGeneraTing Agent (RGTA) has provided encouraging results, accelerating the healing of chronic skin ulcers in diabetes or vascular origin. RGTAs mimic the action of heparin sulfate molecules, breaking the negative repair-destruction cycle occurring in chronic lesions and inhibit proteolytic enzymes in vitro. In the domain of ophthalmology, RGTA has been reported to show encouraging results in the treatment of corneal ulcer and dystrophies of various etiologies.
The Cacicol20 is an RGTA that binds to matrix proteins to protect them from proteolysis; the extracellular matrix microenvironment protection improves the production of signals and growth factors needed for tissue healing. It is supplied as a sterile single-dose solution of alpha 1-6 poly-carboxymethyl glucose sulfate described and synthesized as in US Patent Number 6689741, with dextran T40 and 0.9% sodium chloride as excipients. It contains no component of animal or biological origin, and penetrates into the cornea without crossing Descemet´s membrane (no intraocular penetration). The Cacicol20 has been reported to be effective in treatment of neurotrophic ulcers and persistent epithelial defects which were unresponsive to the common treatment approaches. Therefore, we expect that the Cacicol20 may facilitate the corneal re-epithelialization after PRK.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cacicol20 One drop of Cacicol20 will be applied 4-6 hours after the surgery, in one of the randomly chosen eye, and thereafter one drop daily until the reepithelialization is completed. |
Device: Cacicol20
Cacicol20 is supplied as a sterile single-dose solution of alpha 1-6 poly-carboxymethyl glucose sulfate One drop is instilled at each application to impregnate cornea.
Other Names:
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| Placebo Comparator: Placebo One drop of conservative free artificial tear (Oculac, Thea Laboratories) will be applied to one eye at the same time when Cacicol20 is instilled to the other eye. |
Device: Placebo
Ocluac is artificial tear which contains Hydroxypropylmethyl Cellulose and Sodium Chloride, It is presented in a 0.4 mL vial. One drop is delivered at each application.
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Outcome Measures
Primary Outcome Measures
- Re-epithelialization time [5 days postoperatively]
The patients will be examined daily the changes of reepithelialization area, until the re-epithelialization is complete. The days that takes for complete reepithelialization will be recorded.
Secondary Outcome Measures
- Discomfort during reepithelialization [5 days postoperatively]
Patient´s subjective evaluation of ocular symptoms including pain, burning, stinging, tearing, and photophobia in the two eyes, with score ranging from 0-5 (0 representing absence of symptom and 5 representing unbearable symptom) will be performed daily
Other Outcome Measures
- Postoperative corneal epithelial thickness [1 week and 1 month postoperatively]
Epithelial thickness in the central 2 mm and mid-peripheral (2-5 mm) cornea will be measured in µm using anterior segment spectrum-domain optical coherence tomography
- Inflammatory cytokine [Preoperatively, 24 hours and 72 hours after the surgery]
Concentration of inflammatory cytokines in tears including interleukin 1ß (IL-1ß), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-1RA (receptor antagonist), eotaxin, basic fibroblast growth factor (bFGF/FGF2), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α (MIP-1α/CCL3), MIP-1B, platelet-derived growth factor bb (PDGF-BB), regulated-on-activation normal T cell expressed and secreted (RANTES), tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) will be measured using Multiplex analysis
- Postoperative uncorrected visual acuity [1 week, 1 month postoperatively]
Uncorrected visual acuity will be measured using Snellen visual acuity chart
- Refractive outcome [1 month and 3 months postoperatively]
Subjective manifest refraction will be performed and spherical equivalent (SE) will be recorded in diopters
- Protein expression in tear fluid [Preoperatively, 24 hours and 72 hours after the surgery]
The proteome of tear fluid will be examined through Liquid chromatographymass spectrometry (LC-MS)
- Postoperative complications [1 month and 3 months postoperatively]
The incidence of postoperative complications (infection, haze formation, delayed epithelial healing) will be recorded in percentage
- Postoperative dry eye disease severity level [1 month and 3 months postoperatively]
Clinical dry eye tests including ocular surface disease index (OSDI) questionnaire (score between 0-100, whith higher values presenting more severe dry eye symptoms), tear break-up time (recorded in seconds), ocular surface staining recorded using Oxford scale (0-15, with higher value representing more ocular surface staining), which will be used to determine the dry eye severity level, according to the 2007 Dry Eye Workshop (DEWS) report
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients undergoing bilateral PRK surgeries for treatment of refractive error
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Age over 18 years
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Refractive stability for at least 2 years
Exclusion Criteria:
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Ocular pathology, including keratoconus or suspected keratoconus, glaucoma, and epithelial defects
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Previous corneal surgery
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Systemic disease that might affect corneal wound healing.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- SynsLaser Kirurgi AS
- Laboratoires Thea
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2014/1985/REK sør-øst