Observational study of cenegermin for the treatment of limbal stem cell deficiency associated with neurotrophic keratopathy

Alejandro Arboleda, Christopher N Ta, Alejandro Arboleda, Christopher N Ta

Abstract

Background: Neurotrophic keratopathy (NK) and limbal stem cell deficiency (LSCD) have high morbidity and require aggressive management to prevent permanent vision loss. Cenegermin, a recombinant human nerve growth factor, was approved by the Federal Drug Administration in 2018 for the treatment of NK.

Objectives: To determine the efficacy and safety of cenegermin in the treatment of LSCD associated with NK.

Design: Prospective cohort study.

Methods: Patients diagnosed with LSCD and NK who had failed conventional treatment were enrolled in this prospective open-label study. Patients were treated with cenegermin for 8 weeks. The primary objective was to determine whether the area of abnormal epithelium decreased following treatment. Corneal sensation, visual acuity (VA), and LSCD severity were also evaluated.

Results: Six eyes of 5 patients were included in the study. Cenegermin significantly improved the area of abnormal corneal epithelium in 5 of 6 eyes, measuring 73% of total corneal area at the initial visit and 48% at the final visit (P = .036). Corneal sensation improved in all patients, Cochet-Bonnet aesthesiometry measured 14.7 and 26.7 mm at the initial and final visit, respectively (P = .009). VA improved in 4 out of 6 eyes, with mean initial logMAR VA of 1.67 and final logMAR VA of 1.19 (P = .045). Finally, LSCD grading improved using the Aravena scoring system; however, this difference was not statistically significant (P = .14). One patient presented with an epithelial defect at baseline, which resolved following treatment. No patient withdrew from the study due to adverse effects.

Conclusions: Cenegermin effectively improved the cornea epithelium, VA, and corneal sensation in patients with LSCD and NK who had failed prior treatment. Further studies are necessary to better understand the anatomical changes and to confirm our results with a larger randomized control trial.

Registration: The study was registered at ClinicalTrials.gov with identifier NCT04552730 (https://ichgcp.net/clinical-trials-registry/NCT04552730).

Keywords: cenegermin; limbal stem cell deficiency; neurotrophic keratopathy; oxervate.

Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding, including payment from Dompé farmaceutici, was received by Stanford University. Authors do not have personal affiliations to any funding sources.

© The Author(s), 2022.

Figures

Figure 1.
Figure 1.
Summary of patient visits and time-points. VA, visual acuity.
Figure 2.
Figure 2.
Images showing Subject 2 at the baseline visit (left) and final visit (right). The top row shows an en-face photo of the ocular surface. The baseline image shows conjunctival injection and abnormal epithelium which both improved at the final follow-up. The middle row shows the slit lamp photographs. The bottom row shows improvement in abnormal epithelium with fluorescein staining and cobalt blue light.

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Source: PubMed

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