Fuchs’ Endothelial Corneal Dystrophy: An Overview and Latest Updates

Luai Kawar

Introduction

Fuch’s endothelial corneal dystrophy (FECD) is a progressive inherited endothelial dystrophy. It is characterized by the formation of guttae in Descemet’s membrane and corneal oedema. It remains a significant cause of visual loss worldwide (1). This article aims to provide an overview of the aetiology, pathophysiology, clinical presentation and advances in treatment.

Aetiology

Early-onset FECD is typically inherited in an autosomal dominant manner. COL8A2 is a commonly implicated gene which tends to cause bullous keratopathy early within a few decades of life (2).

The development of late-onset (classic) FECD is multifactorial. Genetic mutations in transcription factor 4, which encodes the E2-2 protein, have been implicated, specifically a trinucleotide expansion in “CTG” (3). Other genes include SLC4A11 which impacts corneal deturgescence as it encodes ion channels that facilitate water resorption. Environmental factors that contribute to FECD include smoking, UV exposure, diabetes and obesity (4).

It is not straightforward to quantify the exact prevalence of FECD, as many patients with corneal guttata do not progress to FECD. It is the most common reason for an endothelial corneal transplant. It is generally more common in Europe and the USA. Women who are aged over 40 are considered at higher risk (5).

Pathophysiology

Via intraocular pressure differences, solutes flow from aqueous humour to the corneal stroma. The endothelial corneal cells are hexagonal in shape and maintain the delicate hydration balance in the stroma. Although exact mechanisms remain unknown, channelopathies in this corneal endothelium is central to the progression of FECD (6). Other potential pathophysiological mechanisms include:

  • Mitochondrial dysfunction resulting in insufficient ATP amounts for endothelial pumps.
  • Oxidative stress and subsequent endothelial apoptosis such as from UV exposure (7).  
  • Abnormal deposition of collagen / other extracellular material resulting in Descemet’s membrane thickening (8).

Degenerating endothelial cells produce hyaline which are called guttata – these are seen clinically on Descemet’s membrane. Over several decades, these degenerating endothelial cells cannot maintain the delicate fluid balance in the corneal stroma resulting in corneal oedema. Eventually, epithelial bullae may form, along with scarring and corneal neovascularisation (4).

Clinical Presentation and Diagnosis

Unlike early-onset FECD, classic disease usually presents over the age of 40. Symptoms typically occur due to corneal oedema including reduced contrast sensitivity, decrease in vision and glare. As FECD progresses, pain may occur as the bullae rupture (which subsides with sub-epithelial fibrosis). In the early stages, symptoms are worse in the morning due to decreased evaporation while asleep. Symptoms may also be worse during humid days (7).

FECD can be diagnosed clinically via  slit-lamp examination. Guttae appear in early stages and haze develops in the cornea with more advanced disease. Eventually, endothelial folds, epithelial cysts/bullae and scarring/neovascularization may be seen (9).

Although useful in the initial evaluation and to follow the course of disease progression, specular microscopy is not mandatory for diagnosis in the presence of diffuse guttae (10). Pachymetry is useful to assess corneal thickness, where central thickness may reach 1 mm (normal 0.5-0.6mm). This can be useful for prognostication and to determine the risks of additional ocular surgery such as cataract (11).

Management

The early morning blurred vision in FECD can initially be managed with hypertonic saline or ointments. In more advanced disease, where the patient is troubled by ocular pain from ruptured bullae, bandage contact lenses may be used (5).

Surgical options for FECD vary based on disease severity and patient suitability. Penetrating keratoplasty (PK), a full-thickness corneal transplant, was once the standard treatment but is now less commonly used due to its slow recovery, higher risk of rejection, and potential complications such as steroid-induced glaucoma (12). Descemet’s Stripping Endothelial Keratoplasty (DSEK) is currently the gold standard for mild to moderate FECD. This procedure replaces only the posterior cornea with donor tissue, leading to better post-operative outcomes compared to PK (6). Descemet’s Membrane Endothelial Keratoplasty (DMEK), developed in 2006, is similar to DSEK but transplants an even thinner layer—only Descemet’s membrane and endothelial cells—resulting in superior visual outcomes (13).

The latest advancement, Descemetorhexis Without Endothelial Keratoplasty (DWEK), also known as Descemet’s Stripping Only (DSO), is an option for select patients with central guttae and a healthy peripheral endothelium. This procedure involves removing a 4mm area of diseased endothelial cells without implanting donor tissue, allowing healthy peripheral cells to migrate and restore vision. The benefits of DWEK include minimal wounds, no risk of graft rejection, and no need for long-term steroid use. However, the central cornea initially swells, temporarily worsening vision, and some patients may still require DMEK or DSEK if healing is unsuccessful (14).

References

  1. Eghrari AO, Gottsch JD. Fuchs’ corneal dystrophy. Expert Review of Ophthalmology [Internet]. 2010 Apr;5(2):147–59. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2897712/
  2. Ong Tone S, Kocaba V, Böhm M, Wylegala A, White TL, Jurkunas UV. Fuchs endothelial corneal dystrophy: The vicious cycle of Fuchs pathogenesis. Progress in Retinal and Eye Research. 2020 May;80:100863.
  3. Jun A, Vedana G, Villarreal Jr. G. Fuchs endothelial corneal dystrophy: current perspectives. Clinical Ophthalmology. 2016 Feb;321.
  4. Majid Moshirfar, Somani AN, Uma Vaidyanathan, Patel BC. Fuchs Endothelial Dystrophy (FED) [Internet]. Nih.gov. StatPearls Publishing; 2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545248/
  5. Feizi S. Corneal endothelial cell dysfunction: etiologies and management. Therapeutic Advances in Ophthalmology [Internet]. 2018 Jan;10:251584141881580. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6293368/
  6. Nanda GG, Alone DP. REVIEW: Current understanding of the pathogenesis of Fuchs’ endothelial corneal dystrophy. Molecular Vision [Internet]. 2019;25:295–310. Available from: https://pubmed.ncbi.nlm.nih.gov/31263352/
  7. Sarnicola C, Farooq AV, Colby K. Fuchs Endothelial Corneal Dystrophy. Eye & Contact Lens: Science & Clinical Practice. 2019 Jan;45(1):1–10.
  8. Zhang J, Patel DV. The pathophysiology of Fuchs’ endothelial dystrophy–a review of molecular and cellular insights. Experimental Eye Research [Internet]. 2015 Jan 1 [cited 2023 Mar 22];130:97–105. Available from: https://pubmed.ncbi.nlm.nih.gov/25446318/
  9. Adamis AP, Filatov V, Tripathi BJ, Tripathi RA mesh C. Fuchs’ endothelial dystrophy of the cornea. Survey of Ophthalmology. 1993 Sep;38(2):149–68.
  10. Hara M, Morishige N, Chikama TI, Nishida T. Comparison of confocal biomicroscopy and noncontact specular microscopy for evaluation of the corneal endothelium. Cornea [Internet]. 2003 Aug;22(6):512–5. Available from: https://pubmed.ncbi.nlm.nih.gov/12883342/
  11. Repp DJ, Hodge DO, Baratz KH, McLaren JW, Patel SV. Fuchs’ Endothelial Corneal Dystrophy. Ophthalmology. 2013 Apr;120(4):687–94.
  12. Moshirfar M, Ding Y, Shah T. A historical perspective on treatment of fuchs’ endothelial dystrophy: We have come a long way. Journal of Ophthalmic and Vision Research. 2018;13(3):339.
  13. Price MO, Giebel AW, Fairchild KM, Price FW. Descemet’s Membrane Endothelial Keratoplasty. Ophthalmology. 2009 Dec;116(12):2361–8.
  14. Franceschino A, Dutheil F, Pereira B, Watson SL, Chiambaretta F, Navel V. Descemetorhexis Without Endothelial Keratoplasty in Fuchs Endothelial Corneal Dystrophy. Cornea. 2021 Dec 8;Publish Ahead of Print.

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