Evaluation of Safety and Efficacy of rhNGF in Patients With Stage 2 and 3 Neurotrophic Keratitis.

Inclusion Criteria

• Patients 18 years of age or older.
• Patients with stage 2 (persistent epithelial defect, PED) or stage 3 (corneal ulcer) neurotrophic keratitis involving only one eye. . Patients with Controlateral eye affected with stage 1 NK can be enrolled.
• PED or corneal ulceration of at least 2 weeks duration refractory to one or more conventional non-surgical treatments for neurotrophic keratitis (e.g., preservative-free artificial tears, gels or ointments; discontinuation of preserved topical drops and medications that can decrease corneal sensitivity; therapeutic contact lenses).
• Evidence of decreased corneal sensitivity (≤ 4 cm using the Cochet-Bonnet aesthesiometer) within the area of the PED or corneal ulcer and outside of the area of the defect in at least one corneal quadrant.
• Best corrected distance visual acuity (BCDVA) score ≤ 75 ETDRS letters, (≥ 0.2 LogMAR, ≤ 20/32 Snellen or ≤ 0.625 decimal fraction) in the affected eye.
• No objective clinical evidence of improvement in the PED or corneal ulceration within the 2 weeks prior to study enrolment.
• Only patients who satisfy all Informed Consent requirements may be included in the study. The patient and/or his/her legal representative must read, sign and date the Informed Consent document before any study-related procedures are performed. The Informed Consent form signed by patients and/or legal representative must have been approved by the IEC/IRB for the current study.
• Patients must have the ability and willingness to comply with study procedures.
• Patients must be eligible for the National Health Insurance (where applicable).

Exclusion Criteria

• Patients with stage 2 or 3 NK affecting both eyes.
• Any active ocular infection (bacterial, viral, fungal or protozoal) or active ocular inflammation not related to NK in the affected eye.
• Any other ocular disease requiring topical ocular treatment in the affected eye during the course of the study treatment period. No topical treatments other than the study medications provided by the study sponsor or allowed by the study protocol can be administered in the affected eye during the course of the study treatment periods.
• Patients with severe vision loss in the affected eye with no potential for visual improvement in the opinion of the investigator as a result of the study treatment.
• Schirmer test without anesthesia ≤3 mm/5 minutes in the affected eye.
• Patients with severe blepharitis and/or severe meibomian gland disease in the affected eye.
• History of any ocular surgery (including laser or refractive surgical procedures) in the affected eye 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). Ocular surgery in the affected eye will not be allowed during the study treatment period and elective ocular surgery procedures should not be planned during the duration of the follow-up period.
• Prior surgical procedure(s) for the treatment of NK (e.g. complete tarsorraphy, conjunctival flap, etc) in the affected eye with the exception of amniotic membrane transplantation. Patients previously treated with amniotic membrane transplantation may only be enrolled two weeks after the membrane has disappeared within the area of the PED or corneal ulcer or at least six weeks after the date of the amniotic membrane transplantation procedure. Patients previously treated with Botox (botulinum toxin) injections used to induce pharmacologic blepharoptosis are eligible for enrolment only if the last injection was given at least 90 days prior to enrolment in the study.
• Use of therapeutic contact lenses or contact lens wear for refractive correction during the study treatment periods in the eye with NK.
• Anticipated need for punctual occlusion during the study treatment period. Patients with punctual occlusion or punctual plugs inserted prior to the study are el