AUTHOR=Balbuena-Pareja Ana , Bogen Chloe S. , Cox Stephanie M. , Hamrah Pedram 

TITLE=Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy

JOURNAL=Frontiers in Neuroscience

VOLUME=17

YEAR=2023

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1210179

DOI=10.3389/fnins.2023.1210179

ISSN=1662-453X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>Neurotrophic Keratopathy (NK) is a neurodegenerative corneal disease that results in diminished corneal sensation. Previous studies have found that Cenegermin 0.002%, a recombinant human nerve growth factor (rhNGF), improves corneal epithelial healing in stage 2 and 3 NK patients. However, rhNGF effect on corneal sensation and nerve regeneration has not been well established. Thus, this study aims to analyze the effect of rhNGF on corneal nerve regeneration using <italic>in vivo</italic> confocal microscopy (IVCM) and on corneal sensitivity in NK patients.</p></sec><sec id="sec2"><title>Methods</title><p>This is a retrospective, longitudinal, case–control study that included patients with NK, treated with rhNGF for at least 4 weeks, with pre- and post-treatment IVCM images available for analysis. Chart reviews were conducted documenting prior medical and surgical history, clinical signs and symptoms, and corneal sensation using Cochet-Bonnet esthesiometry. Corneal nerve parameters were assessed by IVCM. Sex- and age-matched reference controls were selected from a database of healthy subjects for comparison.</p></sec><sec id="sec3"><title>Results</title><p>The study included 25 patients, with 22 (88%) stage 1, two (8%) stage 2, and 1 (4%) stage 3 NK patients, with a median age of 64 years (range: 30–93 years). Total, main, and branch nerve densities [median (range) in mm/mm<sup>2</sup>] were lower in the NK group pre-treatment [2.3 (0.0–21.1); 1.7 (0.0–13.0); 0.5 (0.0–10.2); respectively] vs. controls [22.3 (14.9–29.0); 10.1 (3.2–15.4); and 12.1 (6.2–18.4), (<italic>p</italic> &lt; 0.0001 for all), respectively]. Post-treatment nerve densities increased compared to pre-treatment to 5.3 (0.0–19.4, <italic>p</italic> = 0.0083) for total, 3.5 (0.0–13.2, <italic>p</italic> = 0.0059) for main, and 2.0 (0.0–10.4, <italic>p</italic> = 0.0251) for branch nerves, but remained lower than controls (<italic>p</italic> &lt; 0.0001 for all). Corneal sensation increased from 2.3 ± 1.1 cm pre-treatment to 4.1 ± 1.4 cm post-treatment (<italic>p</italic> = 0.001). Median best corrected visual acuity significantly increased following rhNGF treatment from 0.4 (0.0–1.6) to 0.12 (−0.1 to 1.6) (<italic>p</italic> = 0.007).</p></sec><sec id="sec4"><title>Conclusion</title><p>Patients with NK treated with at least 4 weeks of rhNGF, showed a significant increase in corneal nerve densities after treatment. A significant increase in corneal sensation, as well as best corrected visual acuity, was observed following treatment.</p></sec>