Level of Secretion and the Role of the Nerve Growth Factor in Patients with Keratoconus before and after Collagen Fibre Cross-Linking Surgery

Abstract

The aim of this study was to analyse the concentration of the nerve growth factor (NGF-β) in patients with keratoconus (KC) who are undergoing collagen fibre cross-linking (CXL) surgery in order to better understand the pathogenesis of this disease and observe the molecular changes occurring after the procedure. Among many cytokines, β-NGF seems to play an important role in the healing processes of corneal damage. Therefore, its role in the regenerative process after CXL treatment may affect the course of treatment and its final results. Tear samples from 52 patients were collected in this prospective study. Additionally, the patients also had a number of tests performed, including corneal topography using optical coherence tomography. Flat (K 1), steep (K 2), cylindrical (CYL), and central corneal thickness (CCT) keratometry were assessed. The tear samples were collected, and other tests were performed before the CXL procedure and afterwards, during the 12-month follow-up period. The NGF concentration was measured using the Bio-Plex Magnetic Luminex Assay. Lower levels of NGF-β were detected in the KC patients than in the control group (p < 0.001). The day after the procedure, the NGF-β level was significantly lower (on average by 2.3 pg/mL) (p = 0.037) than before the procedure, after which, the level of the reagent increases, but only in the group with the advanced cone, one month after CXL it was significantly higher (p = 0.047). Regarding the correlation of NGF with topographic measurements, the following were found: NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 before the CXL procedure; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K1 one month after CXL; NGF-β correlates significantly (p < 0.05) and positively (r > 0) with CYL nine months after CXL; and, after twelve months, NGF-β correlates significantly (p < 0.05) and positively (r > 0) with K2 and K1. Corneal sensitivity did not statistically and significantly correlate with the level of NGF-β secretion. Our study suggests that NGF may be crucial in the development and progression of KC as well as in the repair mechanisms after CXL surgery. Further research is needed on the role of NGF and other inflammatory biomarkers for rapid diagnosis and selection of targeted therapy in patients with keratoconus.

Keywords: cross-linking; keratoconus; β-NGF.

Figure 1

Analysis of the level of NGF-β in patients with KC before CXL treatment (0), one day after CXL (1 D), seven days after CXL (7 D), one month after CXL (1 M), three months after CXL (3 M), six months after CXL (6 M), nine months after CXL (9 M), and twelve months after CXL (12 M).

Figure 2

Analysis of NGF-β values one month after CXL divided into the degree of disease advancement (mild, moderate, and severe).

Figure 3

(a) Virtually complete loss of nerves of the subepithelial plexus (SEP) immediately after CXL treatment; (b) initial regeneration of subepithelial plexus nerves approximately one month after CXL; and (c) complete repopulation of the subepithelial plexus nerves approximately six months after CXL treatment.