The primary objective of this exploratory study is to assess preliminary efficacy and safety of rhNGF when administered as eye drops to patients after cataract and refractive surgery. The main criteria for evaluation were: * Change from baseline in SANDE scores for severity and frequency assessed at 8 weeks of treatment (primary efficacy endpoint) * Changes in Cornea vital staining with fluorescein (National Eye Institute \[NEI\] scales) assessed at 8 weeks of treatment (co-primary efficacy endpoint) * Changes in conjunctiva vital staining with fluorescein (NEI scales) (secondary efficacy endpoint); * Changes in Tear Film Break-Up Time (TFBUT)(secondary efficacy endpoint); * Changes in Cochet-Bonnet corneal aesthesiometry (secondary efficacy endpoint); * Changes in Nerve count and morphology at scanning laser in vivo corneal confocal microscopy (only patients who had Laser-Assisted In situ Keratomileusis \[LASIK\] surgery) (secondary efficacy endpoint); * Changes in SANDE scores (face values) for severity and frequency (secondary efficacy endpoint); * Incidence and frequency of treatment-emergent adverse events (TEAEs), assessed throughout the study (safety endpoint).
The proposed phase II study is a single-centre, randomized, double masked, parallel arm, vehicle-controlled trial, designed to evaluate the preliminary efficacy and safety of rhNGF eye drops at 20 µg/ml concentration administered six times daily for 8 weeks in patients who underwent cataract and corneal refractive surgery, both known to damage the corneal sensory nerve plexus. After confirmation of inclusion and exclusion criteria all eligible patients will be randomized at 2:1 ratio to rhNGF or vehicle control treatment with 8 weeks of study treatments administration with 4 weeks Follow-up.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
180
Univ. G. D'Annunzio-Clinica Oftalmologica-Chieti
Chieti, Italy
Change From Baseline in SANDE Scores for Frequency and Severity Assessed at 8 Weeks of Treatment.
The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time frame: Baseline and Week 8
Changes in Cornea Vital Staining With Fluorescein (National Eye Institute [NEI] Scales)
Corneal Staining was derived as the sum of scores of the five corneal sectors (central, superior, inferior, nasal, and temporal) each of which was scored on a scale of 0-3, with a minimum score of 0 and a maximal score of 15 (sum \> 3 out of 15 is abnormal).
Time frame: Baseline and Week 8
Changes in Conjunctiva Vital Staining With Fluorescein (National Eye Institute [NEI] Scales)
Conjunctival Staining was derived as the sum of scores of the conjunctival area (nasal-superior paralimbal, nasal-inferior paralimbal, nasal-peripheral, temporal-superior paralimbal, temporal-inferior paralimbal, temporal-peripheral) with a grading scale of 0-3 and with a minimum score of 0 and a maximal score of 18 (18 indicates the most abnormal score). Grades increase with the number and density of dots. Data for the main eye are reported.
Time frame: From baseline to weeks 4, 8 and 12
Changes in Tear Film Break-Up Time (TFBUT)
The TFBUT measurement was performed after instillation of 5 microliters of 2% sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. The patient was instructed to blink several times to thoroughly mix the fluorescein with the tear film. Data for the main eye are reported.
Time frame: From baseline to weeks 4, 8 and 12
Changes in Cochet-Bonnet Corneal Aesthesiometry
Corneal sensation was measured in both eyes in each of the four quadrants of the cornea using the Cochet Bonnet aesthesiometer before the instillation of any dilating or anesthetic eye drops. The handheld esthesiometer (Cochet-Bonnet) is a device that contains a thin, retractable, nylon monofilament that extends up to 6 cm in length. Variable pressure can be applied by the device by adjusting the length. The monofilament ranges from 60 mm to 5 mm and as the length is decreased the pressure increases from 11 mm/gm to 200 mm/gm. Data for the main eye are reported.
Time frame: From baseline to week 8
Changes in SANDE Scores (Face Values) for Frequency and Severity
The Symptom Assessment in Dry Eye (SANDE) questionnaire is a short questionnaire to evaluate both dry eye intensity and frequency by using a 100 mm visual analogue scale (VAS). The patient symptoms of ocular dryness and/or irritation were quantified on the scale based on two questions that assessed both the severity and frequency of symptoms. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity of symptoms score. The SANDE scale ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.
Time frame: From baseline to weeks 4, 8 and 12
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