Purpose. To evaluate choroidal thickness in patients with coeliac disease (CD) using spectral domain optical coherence tomography (SD-OCT) and to compare the results to normal eyes. Methods. Seventy patients with CD and 70 healthy controls were included in this prospective, comparative study. All participants underwent a complete ophthalmologic evaluation and SD-OCT. Subfoveal, nasal (nasal distance to fovea 500 μm, 1000 μm, and 1500 μm), and temporal (temporal distance to fovea 500 μm, 1000 μm, and 1500 μm) choroidal thickness measurements were performed using SD-OCT. Results. There were no significant differences in sex, ages, and axial lengths between the groups (p=1.0, p=0.601, p=0.314, respectively). The mean choroidal thickness measurements at all predefined measurement point areas were higher in the coeliac group than in the healthy controls (p<0.001). Of all patients with coeliac disease (70 eyes of 70 patients), 64 eyes (84.2%) had uncomplicated pachychoroid (UCP), one eye had pachychoroid pigment epitheliopathy (PPE), and five eyes in the UCP group had PPE in fellow eyes. Conclusion. It is probable that systemic inflammation in coeliac patients causes the enlargement of choroidal vessels and increasing choroidal thickness. PPE, which is believed to be the precursor of central serous chorioretinopathy, can be observed in coeliac patients.

Type 2 brittle cornea syndrome (BCS2) is an inherited connective tissue disease with a devastating ocular phenotype caused by mutations in the transcription factor PR domain containing 5 (PRDM5) hypothesized to exert epigenetic effects through histone and DNA methylation. Here we investigate clinical samples, including skin fibroblasts and retinal tissue from BCS2 patients, to elucidate the epigenetic role of PRDM5 and mechanisms of its dysregulation in disease. First we report abnormal retinal vascular morphology in the eyes of two cousins with BCS2 (PRDM5 Δ exons 9-14) using immunohistochemistry, and mine data from skin fibroblast expression microarrays from patients with PRDM5 mutations p.Arg590* and Δ exons 9-14, as well as from a PRDM5 ChIP-sequencing experiment. Gene ontology analysis of dysregulated PRDM5-target genes reveals enrichment for extracellular matrix (ECM) genes supporting vascular integrity and development. Q-PCR and ChIP-qPCR confirm upregulation of critical mediators of ECM stability in vascular structures (COL13A1, COL15A1, NTN1, CDH5) in patient fibroblasts. We identify H3K9 di-methylation (H3K9me2) at these PRDM5-target genes in fibroblasts, and demonstrate that the BCS2 mutation p.Arg83Cys diminishes interaction of PRDM5 with repressive complexes, including NuRD complex protein CHD4, and the repressive chromatin interactor HP1BP3, by co-immunoprecipitation combined with mass spectrometry. We observe reduced heterochromatin protein 1 binding protein 3 (HP1BP3) staining in the retinas of two cousins lacking exons 9-14 by immunohistochemistry, and dysregulated H3K9me2 in skin fibroblasts of three patients (p.Arg590*, p.Glu134* and Δ exons 9-14) by western blotting. These findings suggest that defective interaction of PRDM5 with repressive complexes, and dysregulation of H3K9me2, play a role in PRDM5-associated disease.

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