Abstract How genetic defects trigger the molecular changes that cause late-onset disease is important for understanding disease progression and therapeutic development. Fuchs’ endothelial corneal dystrophy (FECD) is an RNA-mediated disease caused by a trinucleotide CTG expansion in an intron within the TCF4 gene. The mutant intronic CUG RNA is present at one–two copies per cell, posing a challenge to understand how a rare RNA can cause disease. Late-onset FECD is a uniquely advantageous model for studying how RNA triggers disease because: (i) Affected tissue is routinely removed during surgery; (ii) The expanded CTG mutation is one of the most prevalent disease-causing mutations, making it possible to obtain pre-symptomatic tissue from eye bank donors to probe how gene expression changes precede disease; and (iii) The affected tissue is a homogeneous single cell monolayer, facilitating accurate transcriptome analysis. Here, we use RNA sequencing (RNAseq) to compare tissue from individuals who are pre-symptomatic (Pre_S) to tissue from patients with late stage FECD (FECD_REP). The abundance of mutant repeat intronic RNA in Pre_S and FECD_REP tissue is elevated due to increased half-life in a corneal cells. In Pre_S tissue, changes in splicing and extracellular matrix gene expression foreshadow the changes observed in advanced disease and predict the activation of the fibrosis pathway and immune system seen in late-stage patients. The absolute magnitude of splicing changes is similar in pre-symptomatic and late stage tissue. Our data identify gene candidates for early drivers of disease and biomarkers that may represent diagnostic and therapeutic targets for FECD. We conclude that changes in alternative splicing and gene expression are observable decades prior to the diagnosis of late-onset trinucleotide repeat disease.

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Ophthalmomyiasis externa is an uncommon condition in North America. If not recognized and managed accordingly, it can be complicated by the potentially fatal condition ophthalmomyiasis interna. Ophthalmomyiasis externa is mainly caused by the sheep bot fly Oestrus ovis; thus, it is more common in farming communities. We report a case of ophthalmomyiasis externa in a young woman from Dallas County, Texas, who had no known history of contact with farm animals.

A 100 mm long and 5 mm wide filter paper strip enclosed in a transparent plastic sheath to prevent evaporation was used to determine the time dependence of wetting of the strip in the anesthetized eyes of dry eye patients and age-matched normals. Prior to the measurements, the paper strips were extracted by lipid solvents and marked at every millimeter length. Wetted length data were plotted against time and the resulting wetting curves were analyzed to obtain the time dependence of the tear secretion rate during lacrimation. Every eye studied exhibited an exponentially decaying tear secretion rate that could be characterized by three kinetic parameters per cycle: the initial and final tear secretion rates and the secretion decay coefficient. The eyes of the sicca patients showed a much simpler lacrimation pattern than did the controls: 60% of the dry eyes exhibited a one-cycle lacrimation pattern while only 5% of the normal group did so. The tear secretion kinetic parameters characterizing the lacrimation pattern reduced to one-cycle were compared. Both the dry eyes and the control eyes started to lacrimate at about the same high initial secretion rate. However, the lacrimation rate was found to decrease faster and to a lower final rate in dry eye patients as opposed to normal controls.