Cystic Fibrosis and the eye

Cystic Fibrosis (CF) results from the defective function of CF Transmembrane Conductance Regulator (CFTR), an ion channel which facilitates epithelial chloride secretion. Previous observations of dry eye and abnormal visual function in CF subjects have been considered secondary manifestations due to associated vitamin A deficiency (VAD) and CF-related diabetes (CFRD). However, CFTR is fundamentally present in the corneal, conjunctival and retinal pigment epithelium and the corneal endothelium. The hypothesis for this thesis was that abnormal chloride secretion in CF causes reduced basal tear secretion and abnormal photoreceptor function: these investigations aimed to identify primary and secondary ocular manifestations of CF. Fluorescein tear break-up time was significantly reduced in adult CF subjects compared to healthy controls. Increased signs of ocular surface inflammation and higher tear feming grades were recorded in CF subjects, although differences failed to reach significance. Tear film stability was further reduced in CF adults with VAD suggesting the aetiology of dry eye appears to be a combination of primary and secondary manifestations of the disease. Visual function was essentially normal in CF juveniles but was adversely affected in CF adults compared to controls. Impaired distance and near visual acuity (DVA and NVA), contrast sensitivity (CS), dark adaptation (DA) and colour vision (CV) appeared to be a primary manifestation as differences were exaggerated in subjects with predicted increased levels of CFTR disruption and disease severity. These results provide support for the hypothesis and suggest normal rod and cone photoreceptor function are compromised by abnormal CFTR action. DVA, NVA, CS and DA were significantly affected by CFRD status and DA and CV were similarly reduced in VAD subjects. Therefore, abnormal visual function in CF is further modulated by secondary disease characteristics. These findings present the distinction between primary and secondary ocular manifestations of CF, which is novel to this investigation