Fuchs’ endothelial corneal dystrophy : Genetic aetiology and as a risk factor in cataract surgery

Sammanfattning: Fuchs’ endothelial corneal dystrophy (FECD) is a bilateral, often hereditary degenerative corneal disease, in which the disrupted endothelial cell function causes corneal swelling and reduced vision. An early clinical sign of FECD is corneal guttata, an irregularity of the endothelial layer. Ocular surgery, not least cataract surgery, can lead to endothelial damage and progression of FECD. In Sweden and most Western countries, FECD is the most common indication for corneal transplantation. It has been considered a genetically heterogeneous disease but is increasingly associated with a (CTG)n repeat expansion in transcription factor 4 gene (TCF4). In this thesis, the association between (CTG)n repeat expansion in TCF4 and FECD was investigated, and it was hypothesised that the repeat length correlates with disease severity. The results show that FECD in Northern Sweden is associated with (CTG)n expansion in the TCF4 gene to a large extent. More precisely, expansion with more than 50 repeats in TCF4 was present in nearly 90% of the 85 tested FECD cases compared to only 3.9% in controls, which is the highest published prevalence to date. The disease's severity was associated with the repeat length in the TCF4 gene with an adjusted odds ratio (OR) of 2.13 (95% CI, 1.34-3.39) per repeat length unit. Further, we studied the impact of corneal guttata on cataract surgery outcome, using the data from nationwide eye registries. We show that patients with corneal guttata/FECD benefit from cataract surgery with improved visual acuity and self-assessed visual function, but that they have a greater risk of corneal transplantation and worse results of the cataract surgery than patients without FECD. The risk of corneal transplantation after cataract surgery in patients with corneal guttata was 68 times higher than in patients without corneal guttata. The risk was highest the first year after cataract surgery and decreased after that. Complicated cataract surgery with a dense lens and posterior capsule rupture, both individually and together, increased the risk of corneal transplantation, independent of corneal guttata. In conclusion, most patients with FECD and concomitant symptomatic cataract benefit from cataract surgery. It is not surprising that the risk of corneal transplantation after cataract surgery is increased in patients with FECD, as FECD is an indication for corneal transplantation. Still, the vast majority of FECD patients do not undergo a corneal transplant after cataract surgery. With the results of this thesis as a basis, we recommend, to start with cataract surgery before planning for corneal transplantation in most cases of FECD. Additionally, the surgery should be performed before the lens becomes hazardly dense and with caution to minimise the risk of posterior capsule rupture.