The impact of filaggrin genotype and atopic dermatitis on risk and severity of keratoconus

Filaggrin is a major structural protein in the skin barrier and null mutations in the filaggrin gene (FLG) increase the risk of developing atopic dermatitis (AD). Previous studies report an association between keratoconus (KC) and the presence of AD, and FLG mutated patients with concomitant AD may have a more severe KC. We investigated if FLG genotype and AD correlate to the frequency and severity of KC. One hundred and eight patients were recruited and distributed in four groups based on KC and AD status. Patients with high myopia comprised the reference group. We used the topographical keratoconus classification (TKC), Kmax and central corneal thickness (CCT) to compare the groups and analyzed FLG mutation status by DNA sequencing. In total, 15 patients (14%) in our cohort harbored mutation in FLG. Nine of 49 patients (18%) with AD were FLG mutated whereas 6/59 (10%) without AD were carriers of FLG mutation (P = 0.22). There was no difference in Kmax between KC patients with and without AD (median Kmax 56.9 and 57.6, respectively – P = 0.81). Patients with FLG mutation had a median Kmax of 62.5 whereas FLG wild-type patients had a median Kmax of 56.9, P = 0.29. There was no difference in CCT between FLG mutated KC patients (median CCT 420 µm) and KC patients with FLG wild-type (median CCT 448 µm), P = 0.21. In our cohort, the frequency of FLG mutations was low and genotype equally distributed between patients with and without AD and KC. There was no aggravation in KC severity parameters in FLG mutated patients compared to patients with FLG wild-type. Future studies powered to assess the synergistic influence of AD and FLG genotype may identify patients at risk of severe KC.