Eight months follow-up of corneal nerves and sensitivity after treatment with cenegermin for neurotrophic keratopathy

Abstract

Backgroud Cenegermin (Oxervate, Dompè Farmaceutici, Milan, IT), a recombinant human NGF, is a potentially healing new drug for neurotrophic keratopathy (NK), a rare but challenging disease affecting the cornea. To date, studies that evaluate its mid-term effect on corneal nerves and sensitivity are lacking. Objective To evaluate the recovery and morphology of subbasal corneal nerves in patients treated with Cenegermin for NK and assess their correlation with corneal sensitivity. Methods This prospective, observational case series study was carried out between May 2018 and August 2020 at the Ophthalmic Clinic of the University of Verona. Clinical evaluation, sensitivity, and in vivo confocal microscopy (IVCM) were performed in the central and all four corneal sectors at baseline, the end of therapy (8 weeks), and 2, 4, and 8 months after therapy. Consecutive patients with NK (stage 2–3), treated with Cenegermin (1 drop 6 times daily for 8 weeks), were enrolled. During each visit, Corneal nerve fiber length (CNFL), corneal nerve fiber total branch density (CTBD), corneal nerve fiber fractal dimension (CNFraD) and Cochet-Bonnet esthesiometry (CBE) were measured. Results We enrolled 18 patients. Complete NK healing was noted in 14/18(78%) patients after 8 weeks of treatment; then in 14(78%), 15(83%), and 13(72%) patients at 2-, 4-, and 8-months, respectively. Starting at 8 weeks through 4-month follow-up there was progressive improvement in CBE in all corneal sectors (p ≤ 0.01), which continued thereafter. There was significant corneal nerve regrowth especially in the peripheral cornea: centripetal progression starting at 8 weeks (CNFL and CNFrad) and significant branching starting at 2 months (CTBD), which continued through to the end of follow up. Sector-coupled IVCM and CBE findings correlated at all evaluations (all r ≥ 0.62 starting at 2 months, with highest values in the peripheral sectors). Conclusions After Cenegermin we observed a subbasal corneal nerve regeneration, a recovery of sensitivity and a lasting epithelial healing, suggesting that the effect of its action persists several months after discontinuation in patients with NK.

Meniscus-Shaped Stromal Lenticule Addition Keratoplasty for Corneal Regularization and Thickening in Advanced Keratoconus

“…The corneal nerve fiber length (CNFL) of the subbasal plexus was analyzed with automated ACC Metrics analysis software (Imaging Science and Biomedical Engineering, version 2, Manchester, United Kingdom) to obtain the mean CNFL, which is the total length of nerves expressed in mm/mm 2 . 12…”

“…The corneal nerve fiber length (CNFL) of the subbasal plexus was analyzed with automated ACC Metrics analysis software (Imaging Science and Biomedical Engineering, version 2, Manchester, United Kingdom) to obtain the mean CNFL, which is the total length of nerves expressed in mm/mm 2 . 12 At the 12-month follow-up, all patients underwent a new CL application according to each patient's MRSE and the CDVA with CLs (CL-CDVA) was recorded. Because of the CL intolerance, the CL-CDVA at baseline (T0) was got back from the last patient's medical certification carrying this evaluation.…”

Novel Treatments for Chronic Ocular Surface Pain

“…37 In a prospective, observational case series of 18 individuals with grade 2 or 3 NK, individuals were treated with cenegermin 6 times daily. 38 After 8 weeks, epithelial defects healed in 78% of individuals and IVCM revealed increased corneal nerve fiber length particularly in the superior [posttreatment: 3.66 mm/mm 2 (interquartile range (IQR): 6.63) vs. pretreatment: 0 mm/mm 2 (IQR 2.82), P < 0.01] and temporal [posttreatment: 4.63 mm/mm 2 (IQR: 7.26) vs. pretreatment: 1.99 mm/mm 2 (IQR 3.74), P = 0.01] corneal quadrants. Fortunately, nerve length continued to improve at 4 and 8 months follow-up after terminating 8 weeks of therapy.…”

“…37 In a prospective, observational case series of 18 individuals with grade 2 or 3 NK, individuals were treated with cenegermin 6 times daily. 38…”

Topical Decorin Reduces Corneal Inflammation and Imparts Neuroprotection in a Mouse Model of Benzalkonium Chloride-induced Corneal Neuropathy

“… 12 , 13 Topical application of recombinant human nerve growth factor in these clinical trials primarily aims to promote corneal epithelial healing; however, recent evidence supporting a direct neurogenerative effect of recombinant human nerve growth factor has been reported in a prospective, observational clinical study, although control group data were not available. 14 …”