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This is a prospective, randomized, double-blinded, controlled clinical trial designed to evaluate the efficacy and safety of topical losartan in improving visual acuity, contrast sensitivity and reducing corneal densitometry, corneal aberrations and corneal scarring severity in adult patients with corneal scars of different etiologies. Participants will be randomly assigned to receive either topical losartan 0.8 mg/mL or placebo eyedrops 6 times per day for six months.
Corneal scarring is a significant cause of visual impairment worldwide, with limited conservative treatment options. Corticosteroids are commonly used but are associated with important adverse effects. Losartan, an angiotensin II receptor blocker, has demonstrated antifibrotic effects through inhibition of TGF-β signaling in experimental studies.
This study aims to evaluate the safety and efficacy of topical losartan in improving visual function and corneal transparency in patients with corneal scarring fibrosis. Outcomes include changes in best-corrected visual acuity measured using the ETDRS chart, contrast sensitivity with FACT chart, corneal scar area calculated with ImageJ, corneal density assessed by Scheimpflug corneal densitometry, corneal aberrations using Zernike Analysis and clinical corneal scar severity evaluated using slit-lamp biomicroscopy with Fantes haze grading, compared with placebo. A total of 46 adult patients with stable corneal scars will be enrolled and followed for six months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Topical losartan | Active Comparator | Drug: Topical Losartan 0.8 mg/ml ophthalmic Solution, one drop applied six times daily for six months |
|
| Placebo | Placebo Comparator | Drug: Balanced saline solution ophthalmic drops, one drop applied six times daily for six months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Topical losartan | Drug | Drug: Topical Losartan 0.8 mg/ml ophthalmic solution, one drop applied six times daily for six months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Best Corrected Visual Acuity (BCVA) | BCVA measured using ETDRS chart and reported in LogMAR units. | Baseline to 6 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Contrast Sensitivity | Contrast sensitivity will be evaluated using FACT chart. | Baseline to 6 months. |
| Change in Corneal Haze Severity | Corneal haze will be assessed using the Fantes Corneal Haze Grading Scale, evaluated by slit-lamp biomicroscopy. The scale ranges from 0 to 4. Grade 0: Clear with no opacity seen by any method of microscopic slit-lamp examination. Grade 0.5: Trace or faint haze seen only by indirect, broad tangential illumination. Grade 1: Haze of minimal density seen with difficulty with direct or diffuse examination. Grade 2: Mild haze easily visible with direct focal slit-lamp illumination. Grade 3: Moderate opacity that partially obscures details of the iris. Grade 4: Severe opacity that completely obscures the details of intraocular structures. The minimum possible score is 0 and the maximum possible score is 4. Higher scores indicate greater corneal opacity and worse clinical outcome. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Karim Mohamed-Noriega, Dr. med. | Contact | +52 8113404960 | 8514 | karim.mohamednrg@uanl.edu.mx |
| Name | Affiliation | Role |
|---|---|---|
| Karim Mohamed-Noriega, Dr. med. | Universidad Autonoma de Nuevo Leon | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ophthalmology Department | Recruiting | Monterrey | Nueo Leon | 64460 | Mexico |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | COZAAR® (losartan potassium) tablets, for oral use Initial U.S. Approval: 1995 . FDA | ||
| Background | PLM. (n.d.). COZAAR - Comprimidos. Medicamentos PLM. Recuperado el 9 de febrero de 2025, de https://www.medicamentosplm.com/Home/productos/cozaar.comprimidos/128/101/77344/25 | ||
| 19571282 | Background | Mauer M, Zinman B, Gardiner R, Suissa S, Sinaiko A, Strand T, Drummond K, Donnelly S, Goodyer P, Gubler MC, Klein R. Renal and retinal effects of enalapril and losartan in type 1 diabetes. N Engl J Med. 2009 Jul 2;361(1):40-51. doi: 10.1056/NEJMoa0808400. | |
| 18800452 |
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| ID | Term |
|---|---|
| D065306 | Corneal Injuries |
| D003318 | Corneal Opacity |
| ID | Term |
|---|---|
| D005131 | Eye Injuries |
| D005151 | Facial Injuries |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
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Not provided
| ID | Term |
|---|---|
| D019808 | Losartan |
| ID | Term |
|---|---|
| D001713 | Biphenyl Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
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Parallel Assignment
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| Placebo Control | Drug | Drug: Balanced saline solution ophthalmic drops, one drop applied six times daily for six months. |
|
| Baseline to 6 months. |
| Change in Corneal Scar Density | Corneal scar density will be quantitatively measured using Scheimpflug corneal tomography corneal densitometry and reported in grayscale units (GSU). | Baseline to 6 months |
| Change in Corneal Scar Area | The area of corneal scarring will be measured using slit-lamp corneal photography and analyzed with Image J software, reported in square millimeters (mm²). | Baseline to 6 months. |
| Change in corneal aberrations | Corneal scar density will be quantitatively measured using Scheimpflug corneal tomography corneal Zernike Analysis reported micron. | Baseline to 6 months. |
| Change in Intraocular Pressure | Intraocular pressure will be measured using Goldmann applanation tonometry to monitor ocular safety. | Baseline to 6 months. |
| Change in corneal pachymetry | Corneal pachymetry will be measeured using optical coherence tomography. | Baseline to 6 months. |
| Corneal scar depth | Corneal scar depth will be evaluated using optical coherence tomography line scan. | Baseline to 6 months. |
| Treatment Adverse Events | Treatment adverse events will be assessed based on patient-reported ocular discomfort and recorded adverse events during follow-up visits. | Baseline to 6 months. |
| Treatment Adherence | Treatment adherence will be assessed based on daily patient adherence report. | Baseline to 6 months. |
| Background |
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| D009422 |
| Nervous System Diseases |
| D003316 | Corneal Diseases |
| D005128 | Eye Diseases |
| D014947 | Wounds and Injuries |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013777 | Tetrazoles |