La Fuchs endothelial dystrophy is a progressive eye disease characterised by degeneration of the endothelial cells of the cornea, which are essential for maintaining transparency and good vision quality.
Symptoms and Diagnosis
When the cells of the corneal epithelium degenerate, fluid accumulation and oedema formation can cause blurred vision and, in advanced cases, blindness.
Initial symptoms can easily be underestimated, as patients often experience blurred vision upon waking, which improves during the day as the cornea becomes oedematous during sleep and drains during the day.
Early diagnosis and management can slow down the progression of the disease, but in advanced stages, a cornea transplant.
Diagnosis requires a complete eye examination. The ophthalmologist can use a biomicroscope to observe the cornea and assess the presence of guttae, small protuberances on the posterior surface of the cornea, which are an indicator of the disease.
Another common test is optical coherence tomography (OCT), which provides detailed images of the cornea and helps determine the extent of damage.
One genetic screening may be recommended to confirm the presence of associated mutations.
News from Genetics
A study published in JAMA Ophthalmology reported important news on the role of the TCF4 genewhich is involved, as its repeated expansions are present in a significant percentage of patients.
Mutations in the TCF4 gene lead to abnormal protein production, contributing to degeneration of corneal endothelial cells.
Length CTG18.1
Another important genetic aspect is the length of the repeats CTG18.1as longer repetitions are associated with faster progression and more severe symptoms of Fuchs' dystrophy. This result suggests that the measuring the length of CTG18.1 repetitions could be a useful prognostic indicator.
The new findings, moreover, offer new targets for research into drugs that modulate gene expression.
Demographic Factors and Risk
Demographic factors play a significant role in Fuchs' endothelial dystrophy.
Gender differences
Gender differences are important, as women seem to be more affected than men, especially in the absence of specific genetic expansions.
This disparity may be due to biological or hormonal factors that influence disease progression.
Therapeutic strategies must, therefore, consider gender specificities to improve efficacy and reduce side effects.
Age and Other Factors
Age is a risk factor, as Fuchs dystrophy is more common in older adults, but can also occur at a younger age, especially in the presence of genetic mutations.
Other factors that may influence risk include family history and exposure to certain environmental factors. The combination of these factors can accelerate disease progression.
Therapeutic Strategies
New genetic discoveries pave the way for innovative therapeutic strategies based on a patient's specific genetic mutations to guide the development of personalised treatments.
Therapies targeting gene mutations TCF4 could offer new possibilities for slowing or halting the progression of the disease.
Implications for the Future of Research
Recent genetic discoveries offer numerous opportunities for new clinical studies to evaluate the effectiveness of gene therapy, the use of drugs that modulate gene expression or new surgical techniques. Subsequent clinical studies will then be essential to confirm the safety and efficacy of these new treatments.
Personalised Care Perspectives
Personalised treatment represents the future of treatment for Fuchs' dystrophy and research will have to focus on integrating genetic data into standard treatment protocols.
The future: collaboration & innovation
Collaboration between scientists is crucial for the advancement of ophthalmic research and, in the case of Fuchs' dystrophy, future development will depend on the ability to combine genetics, technological innovations - such as artificial intelligence and computational biology - and clinical medicine to develop cutting-edge treatments for patients.
- Liu S, Sadan AN, Bhattacharyya N, et al. Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity. JAMA Ophthalmol.Published online March 13, 2025. doi:10.1001/jamaophthalmol.2025.0109
- Prašnikar E, Stunf Pukl S. How "Omics" Studies Contribute to a Better Understanding of Fuchs' Endothelial Corneal Dystrophy. Curr Issues Mol Biol. 2025 Feb 20;47(3):135. doi: 10.3390/cimb47030135. PMID: 40136389; PMCID: PMC11941302.