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

Emilio Pedrotti; Erika Bonacci; Chiara Chierego; Alessandra De Gregorio; Tiziano Cozzini; Tommaso Brighenti; Grazia Caldarella; Giovanlorenzo Pastore; Adriano Fasolo; Giorgio Marchini

doi:10.1186/s13023-022-02237-5

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

Orphanet J Rare Dis. 2022 Feb 21;17(1):63. doi: 10.1186/s13023-022-02237-5.

Affiliations

¹ Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Policlinico G.B. Rossi, P.Le L.A, Scuro 10, 37134, Verona, VR, Italy.
² Ophthalmic Unit, San Bassiano Hospital, Via dei Lotti, 40, 36061, Bassano del Grappa, Italy.
³ Ophthalmic Unit, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Policlinico G.B. Rossi, P.Le L.A, Scuro 10, 37134, Verona, VR, Italy. tizianocozzini@gmail.com.
⁴ The Veneto Eye Bank Foundation, Padiglione G. Rama, Via Paccagnella 11, 30174, Zelarino Venezia, Italy.

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.

Keywords: Cenegermin; Corneal nerves; Corneal sensitivity; In vivo confocal microscopy; Nerve growth factor; Neurotrophic keratopathy; rhNGF.

Publication types

Observational Study

MeSH terms

Cornea / innervation
Corneal Dystrophies, Hereditary*
Follow-Up Studies
Humans
Nerve Growth Factor* / adverse effects
Nerve Growth Factor* / therapeutic use
Ophthalmic Solutions / therapeutic use
Prospective Studies
Recombinant Proteins

Substances

Ophthalmic Solutions
Recombinant Proteins
Nerve Growth Factor
cenegermin