Deep Optic Nerve Head Structural Alterations in Adults with Cystic Fibrosis

Background: Cystic fibrosis (CF) is a systemic genetic disorder characterized by chronic inflammation, hypoxia, and metabolic imbalance that may affect neural and microvascular structures. While previous studies have evaluated superficial optic nerve head (ONH) parameters in CF, deep ONH structures, particularly the lamina cribrosa (LC), remain insufficiently explored. This study aimed to assess both superficial and deep ONH morphology in adults with CF using swept-source optical coherence tomography (SS-OCT). Methods: This observational case–control study included 34 CF individuals and 34 age- and sex-matched healthy controls. CF patients were examined at baseline and after 12–18 months of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy. All participants underwent comprehensive ophthalmic examination and SS-OCT imaging. Assessed parameters included peripapillary retinal nerve fiber layer (RNFL) thickness, lamina cribrosa thickness (LCT), and lamina cribrosa depth (LCD). Between-group comparisons were performed using ANCOVA adjusted for axial length (AL) and IOP. Results: After adjustment for AL and IOP, total RNFL thickness did not differ significantly between the CF group and controls (F(1,92) = 0.363, p = 0.548). However, CF patients demonstrated significantly reduced central LCT (170.2 µm [95% CI 162.2–178.2] vs. 214.6 µm [95% CI 208.6–220.7]; F(1,91) = 72.205, p < 0.001) without markedly altered LCD (425.5 µm [95% CI 390.4–454.2] vs. 354.7 µm [95% CI 329.6–379.8]; F(1,94) = 10.090, p = 0.099) compared with controls. Intraocular pressure was also higher in CF patients (17.50 mmHg [95% CI 16.60–18.41] vs. 15.87 mmHg [95% CI 15.19–16.55]; F(1,83) = 7.660, p = 0.007). Longitudinally, total RNFL thickness decreased from 106.5 µm (IQR 15.25) to 102.0 µm (IQR 15.5) following therapy (z = 3.488, p < 0.001), while LCT (p = 0.364) and LCD (p = 0.660) remained stable. Conclusions: CF is associated with significant alterations in deep ONH structures, characterized by thinner LC, independent of ocular biometry. In contrast, superficial RNFL differences appear to be largely influenced by AL. LC parameters, particularly LCT, may represent potential structural markers of systemic involvement in CF, pending further validation.