An 8-week Follow-up to Evaluate the Renewal of Corneal Nerves Structure and Function in Patients With Neurotrophic Keratopathy Treated With Recombinant Human Nerve Growth Factor (rhNGF) Eyedrops

In Vivo Evaluation of Corneal Nerves and Epithelial Healing After Treatment With Nerve Growth Factor for Neurotrophic Keratopathy

A prospective, longitudinal, cross-sectional, observational Study with a 8-week Follow-up to evaluate the renewal of corneal nerves structure and function in patients with Neurotrophic Keratopathy treated with recombinant human Nerve Growth Factor (rhNGF) eyedrops.

Study Overview

• Status: Completed
• Conditions: Neurotrophic Keratopathy
• Intervention / Treatment: Drug: Cenegermin, recombinant human Nerve Growth Factor (rhNGF) eyedrops

Detailed Description

This Study shows that topical treatment with Recombinant Nerve Growth Factor (rhNGF) improved corneal sensitivity and increased sub-basal nerves density, promoting corneal healing of persistent epithelial defects and corneal ulcers in patients with stage 2 and 3 NK

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• Italy
  • Chieti, Italy, 66013
    • Ophtalmology Clinic, G.d'Annunzio University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

18 patients (9 males and 9 females) were recruited from the Ocular Surface Service of G. d'Annunzio University of Chieti- Pescara and from the Division of Clinical Neuroscience, Department of Ophthalmology, University of Nottingham.

Description

Inclusion Criteria:

• Patients with documented moderate or severe neurotrophic keratopathy based on a recent new classification of NK, refractory to conventional non surgical treatments. The diagnosis was made on medical and ophthalmological history, slit lamp examination, aesthesiometry, in vivo confocal microscopy.
• Decreased corneal sensitivity on the area of corneal defect and on superior, inferior, nasal and temporal quadrants (≤ 4 cm using the Cochet-Bonnet aesthesiometer)
• Patients who satisfy all Informed Consent requirements. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed
• Patients with ability to understand and perform the treatment.

Exclusion Criteria:

• active infective keratitis or inflammation not related to NK in the affected eye.
• presence of corneal dystrophies.
• presence of glaucoma.
• Any other ocular disease requiring topical ocular treatment during the course of the study treatment period.
• History of any ocular surgery (including laser or refractive surgical procedures) within the three months before study enrolment. (An exception to the preceding statement will be allowed if the ocular surgery is considered to be the cause of the stage 2 or 3 NK).
• patients with known hypersensitivity to one of the components of the study or procedural medications (e.g. anaesthetic drops, fluorescein).
• Females currently pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
rhNGF group; Therapeutic contact lens use was discontinued during the duration of the study. Patients underwent clinical examination with corneal fluorescein staining, Schirmer I tear test, assessment of corneal sensitivity with Cochet-Bonnet aesthesiometer and morphological examination of the nerves by In Vivo Confocal Microscopy (IVCM) at baseline and after 4 and 8 weeks of treatment. Changes in the corneal epithelium and stroma were evaluated by slit lamp biomicroscopy and photo documentation of the cornea after fluorescein staining.	Drug: Cenegermin, recombinant human Nerve Growth Factor (rhNGF) eyedrops; rhNGF 20µg/ml (Cenegermin) eyedrops, 1 drop every 2 hours (6 times a day) for 8 weeks. Patients underwent clinical examination with corneal fluorescein staining, Schirmer I tear test, assessment of corneal sensitivity with Cochet-Bonnet aesthesiometer and morphological examination of the nerves by In Vivo Confocal Microscopy (IVCM) at baseline and after 4 and 8 weeks of treatment; Other Names: Oxervate
control comparator group; control comparator group was matched for age and gender and underwent assessment of corneal sensitivity with Cochet-Bonnet aesthesiometer and morphological examination of the nerves by In Vivo Confocal Microscopy (IVCM) at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of sub-basal nerve density, diameter and number of nerve branches	evaluated by In Vivo Confocal Microscopy (IVCM). Confocal microscopic scanning was focused on central cornea and superior, inferior, nasal and temporal quadrants; for each zone, 5 frames at the level of the epithelium and basal lamina were obtained. Corneal sub-basal nerve morphology and density was traced using NeuronJ, plug-in of ImageJ. Nerve regeneration rate was calculated.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Corneal Sensitivity	measured by the Cochet-Bonnet aesthesiometer at 4 and 8 weeks after start of the treatment. Corneal sensitivity is measured in each patient in cm. the filament was applied on the area of corneal defect and on superior, inferior, nasal and temporal quadrants.	8 weeks
Changes of persistent epithelial defect and corneal ulcers	determined by corneal fluorescein staining at 4, 8 weeks as defined by the central reading center on clinical pictures	8 weeks

Collaborators and Investigators

• Sponsor: G. d'Annunzio University
• Investigators: Principal Investigator: Leonardo Mastropasqua, Professor, Ophtalmology Clinic, G. d'Annunzio University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): November 30, 2018

Study Registration Dates

• First Submitted: February 28, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 3, 2020

Study Record Updates

• Last Update Posted (Actual): March 5, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Pharmaceutical Solutions; Ophthalmic Solutions; Mitogens
• Other Study ID Numbers: UChieti01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No