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

Completed

• Conditions: Neurotrophic Keratopathy
• Interventions: Drug: Cenegermin, recombinant human Nerve Growth Factor (rhNGF) eyedrops

• Registration Number: NCT04293549
• Lead Sponsor: G. d'Annunzio University

Brief Summary

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.

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 Timeline

• Study Start: 2018-03-01
• Primary Completion: 2018-11-30
• Study Completion: 2018-11-30
• Study First Submitted: 2020-02-28
• Status Verified: 2020-03
• Study First Submitted QC: 2020-03-02
• Study First Posted: 2020-03-03
• Last Update Submitted: 2020-03-03
• Last Update Posted: 2020-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
rhNGF group	Cenegermin, recombinant human Nerve Growth Factor (rhNGF) eyedrops	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.

Primary Outcome Measures

Name	Time	Method
Changes of sub-basal nerve density, diameter and number of nerve branches	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Changes in Corneal Sensitivity	8 weeks	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.
Changes of persistent epithelial defect and corneal ulcers	8 weeks	determined by corneal fluorescein staining at 4, 8 weeks as defined by the central reading center on clinical pictures

Trial Locations

Locations (1)

Ophtalmology Clinic, G.d'Annunzio University; 🇮🇹 Chieti, Italy