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Ophthalmology and Visual Sciences

Fuchs Endothelial Corneal Dystrophy:
From One Medical Student to Another

Fuchs Endothelial Corneal Dystrophy:
From One Medical Student to Another

Contributors: Bryce Shonka, BS; Aaron D. Dotson, MD; Mark A. Greiner, MD

The University of Iowa
Department of Ophthalmology and Visual Sciences

Posted January 22, 2024


Fuchs Endothelial Corneal Dystrophy (FECD) is a corneal dystrophy affecting primarily the deepest layer of the cornea, known as the corneal endothelium. It is the most common corneal dystrophy, affecting 4% of the American population over the age of 40, [1] and is the most common indication for corneal transplantation in the US. [2] As this condition is frequently encountered (especially in cornea clinic), it is a great topic for medical students to be familiar with prior to their ophthalmology rotations.


To understand how FECD affects vision, an understanding of corneal anatomy is essential. The cornea is the transparent “window” that allows light to enter the eye and reach the photoreceptors in the retina. The cornea, combined with the air-tear interface, produces approximately 70 percent of the eye’s refractive power.[3] The cornea is comprised of five layers, consisting of cellular and acellular components. From superficial to deep the layers are as follows (Figure 1):

  • Epithelium: The outermost layer of the cornea is the epithelium, which is made up of 5-7 layers of nonkeratinized stratified squamous cells.[1]
  • Bowman membrane: Deep to the epithelium is Bowman membrane, which consists of collagen and proteoglycans and helps maintain the shape of the cornea.[2] This layer is not the true basement membrane of the corneal epithelium.
  • Stroma: Next is the largest corneal layer, the stroma, which provides most of the corneal structure and accounts for 90% of corneal thickness. The stroma is transparent as a result of the precise organization of its keratocytes (stromal cells) and extracellular matrix (primarily collagen types I, V, and VI), along with strict regulation of its water content.[3] Ideal hydration of the stroma is 78% water, which provides optimum corneal clarity.
  • Descemet membrane: Deep to the stroma is Descemet membrane, which is the basement membrane for the corneal endothelium, and is made up of collagen types IV and VIII as well as laminin.[2]
  • Endothelium: Finally, the innermost layer, the corneal endothelium, is comprised of a monolayer of neural crest derived cells that are post-mitotic, meaning they have no ability to regenerate.[4]When healthy, these cells have a characteristic hexagonal shape (Figure 2). The corneal endothelium can be thought of as having both “barrier” and “pump” functions, and functions to counteract the passive leakage of aqueous humor through tight junctions into the stroma. This process is essential for maintaining corneal transparency and requires cellular energy to maintain.[3,5,6]
Pictograph demonstrating the 5 layers of the cornea.
Figure 1. Pictograph demonstrating the 5 layers of the cornea. The cornea has an average central thickness of 540 micrometers. Layers from anterior to posterior: epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. Source: [1]
Specular microscopy demonstrating healthy corneal endothelial cells with characteristic hexagonal morphology.  Note, endothelial cell density is within a normal range for an adult patient (2646 cells/mm2 on the right, 3175 cells/mm2 on the left).
Figure 2. Specular microscopy demonstrating healthy corneal endothelial cells with characteristic hexagonal morphology. Note, endothelial cell density is within a normal range for an adult patient (2646 cells/mm2 on the right, 3175 cells/mm2 on the left).


Though it is a normal part of aging, endothelial cell death is severely exacerbated in FECD.[2] Since corneal endothelial cells do not regenerate, neighboring cells must migrate and fill gaps in this cell layer.[3] This leads to a loss in barrier and pump function, and disrupted regulation of proper corneal hydration. As endothelial cells die, remaining cells migrate, grow, and lose their characteristic hexagonal shape in order to fill in these gaps. This behavior results in the characteristic polymegathism and pleomorphism, respectively, that is observed on specular microscopy in patients with FECD (Figure 3). Additionally, FECD is a disease characterized by abnormal extracellular matrix deposition, which leads to the buildup of collagen excrescences, known as guttae, that accumulate, initially centrally, on the endothelium and can be detected on slit lamp examination.[4] These degenerative changes become visually significant over time, particularly as poor pump function leads to stromal edema that decreases corneal transparency and scatters light.

posterior vitreous detachment
Figure 3. Specular microscopy of the right and left eye of an FECD patient demonstrating diffuse guttae, decreased endothelial cell density, and increased cellular pleomorphism with loss of hexagonality.

The condition is polygenic, meaning there have been many genes identified that can cause FECD. Of these, the TCF4 intronic trinucleotide repeat expansion is the most common genotype, and typically leads to a later onset of disease (e.g., manifesting in the 6th and 7th decades of life).[2] The TCF4 gene encodes for transcription factor 4, a broadly expressed transcription factor that may play a role in nervous system development. Additionally, COL8A2, which encodes the alpha 2 chain of type VIII collagen, has been identified as a gene for early-onset FECD (e.g., 2nd decade of life).[3] The mechanism of cell-death is not yet fully known but involves increased vulnerability to oxidative stress. [4-7]


The Krachmer grading scale can be used to classify severity of FECD and track progression of the disease. Grading is based on the characterization of guttae on slit lamp examination.[8]

  • Grade 1: 0-12 central guttae (1+ guttae)
  • Grade 2: Greater than 12 central nonconfluent guttae (2+ guttae)
  • Grade 3: 1-2 mm of confluent central guttae (3 + guttae)
  • Grade 4: 2-5 mm of confluent central guttae (4+ guttae)
  • Grade 5: Greater than 5 mm of confluent central guttae or G4 with stromal or epithelial edema

Once 4+ guttae is noted on exam, stromal edema, stromal haze, epithelial edema, and epithelial bullae (blisters on the epithelial surface resulting from endothelial pump dysfunction) will be tracked over time, as the presence of visually significant edema is an indication for surgical intervention.


Early symptoms of FECD may include blurry or hazy vision in the morning that improves throughout the day. This diurnal variation occurs because of stromal fluid accumulation overnight while the eyes are closed, limiting surface evaporation. As the disease progresses, blurriness improves less throughout the day, and patients may complain of glare in dim lights, halos, decreased contrast sensitivity, and possible pain from ruptured bullae or microcystic edema.[2,3]

Examination and Testing

Slit lamp exam

Early in the disease, the only finding may be guttae, which often start centrally and then spread peripherally (Figure 4 A,B,E,F). The easiest way to appreciate subtle guttae is either by indirect illumination or retroillumination on slit lamp exam. As the disease progresses, stromal edema becomes noticeable (Figure 4 C,D) and can be visualized by direct illumination with a narrow parallelepiped slit. As stromal edema worsens, bullous keratopathy can be noted on exam. For patients with extreme pain, surface staining of the cornea with fluorescein can highlight areas of ruptured bullae, which may indicate a need for antimicrobial coverage to allow for healing of these epithelial defects. In end-stage FECD, exam findings include subepithelial fibrosis, scarring, and peripheral superficial vascularization as a result of long-standing edema and cellular damage.[2]

slit lamp photo of the right and left eyes
Figure 4. Slit lamp photographs of the right (A, C, E) and left (B, D, F) eye demonstrating diffuse central and peripheral guttae by retroillumination (A, B), corneal haze and edema with 2+ Descemet folds (C) and trace Descemet folds (D). Stromal edema and central guttae are redemonstrated in panels E and F.


Pachymeters utilize ultrasound energy in order to measure central corneal thickness. While FECD is a clinical diagnosis, pachymetry is both supportive in the diagnosis and useful for tracking disease progression, as the cornea will progressively thicken as more endothelial cells are lost and the stroma becomes more edematous.[3] For context, a normal, healthy cornea has a central corneal thickness of 545 micrometers.

Specular microscopy

Specular microscopy is an imaging tool for assessing endothelial cell density. While not necessary for the diagnosis, it can be supportive and can aid in tracking changes over time. Endothelial cell counts will decrease as FECD progresses (Figure 3).[3] For context, a normal healthy cornea in an adult has an endothelial cell density of approximately 2000-3000 cells/mm2. Additionally, specular microscopy allows visualization of the aforementioned polymegathism, pleomorphism, and loss of hexagonality changes that are characteristic of endothelial cells in FECD.


Medical Management

There are currently no definitive medical treatments available for FECD. However, patients can use hypertonic saline drops (i.e. Muro128) for symptomatic relief. This hypertonic solution creates a concentration gradient which draws fluid out from the anterior stroma, thereby alleviating early morning blurred vision and photophobia/pain caused by epithelial edema. Unfortunately, hypertonic saline drops are incapable of clearing a cornea with severe or posterior stromal edema. For this reason, surgery (partial thickness corneal transplantation, i.e. endothelial keratoplasty (EK) is the mainstay of treatment.[3] Historically, full thickness corneal transplantation, or penetrating keratoplasty (PK), was the only available surgical treatment for these patients. PK was reserved for patients with end-stage disease, characterized by severe corneal edema, scarring, bullous keratopathy, and neovascularization. However, since the development of EK techniques in the late 1990s and early 2000s, which are less invasive and have lower rates of complications, PK is no longer used as the initial surgical management for FECD. Currently, patients with FECD are offered EK when they have developed visually significant corneal edema but do not have significant, permanent stromal scarring that would compromise visual outcomes of the surgery.


Keratoplasty, or corneal transplantation, involves replacing damaged portions of the patient’s cornea with functional graft tissue from a deceased donor (i.e. allogeneic transplantation). The corneal endothelium is the damaged component in patients with FECD. Therefore, transplantation in these patients involve partial thickness grafts of the endothelium, known as endothelial keratoplasty (EK) (Figure 5). Examples of endothelial keratoplasty include:

  • Descemet membrane endothelial keratoplasty (DMEK) – Donor tissue consisting of only endothelium and Descemet membrane.[3]
  • Descemet stripping automated endothelial keratoplasty (DSAEK) – Donor tissue consisting of endothelium, Descemet membrane, and posterior stroma.[4]
slit lamp photo of the right and left eyes
Figure 5. Schematic portraying the region of corneal tissue transplanted (red) for various modern keratoplasty techniques, including penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK), and Boston Type I Keratoprosthesis (KPRO). For modern surgical treatment of FECD, DSAEK and DMEK are the two techniques used. Source:[5]

Both EK techniques require the use of a gas bubble into the anterior chamber to help position the graft against host tissue. EK, particularly DMEK, has a faster rate of vision recovery, better quality of vision, and a lower rejection rate than DSAEK. For this reason, DMEK is the preferred technique for corneal transplantation in the absence of complex anatomy (e.g., prior glaucoma surgery or prior retinal surgery).[6] DMEK surgical video available at ( While visual outcomes post-transplant are typically quite good, there is always a risk of graft detachment, failure, or rejection, even years down the road. Some patients may require multiple transplants in their lifetime, and most will require prophylactic corticosteroid drops (i.e. prednisolone acetate 1%) for the rest of their life to prevent rejection.[7] Discussion on the identification and management of graft rejection and failure is beyond the scope of this article.


  1. Turner R MS, Kitzmann A. Laser Vision Correction: From one Medical student to another. 2011, tutorialsLaser-Vision-Correction-tutorial
  2. Field MGG, G.; Dotson, A. D; Witsberger, E. M.; Sales, C. S.; Greiner, M. A. . Fuchs’ Endothelial Corneal Dystrophy. 2023,
  3. Price MO, Giebel AW, Fairchild KM, Price FW, Jr. Descemet's membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology 2009;116(12):2361-2368. [PMID 19875170]
  4. Bahar I, Kaiserman I, McAllum P, Slomovic A, Rootman D. Comparison of Posterior Lamellar Keratoplasty Techniques to Penetrating Keratoplasty. Ophthalmology 2008;115(9):1525-1533
  5. Donaghy CL VJ, Greiner MA. An Introduction to Corneal Transplantation. 2015,
  6. Robert S. Feder MD. 2022-2023 Basic and Clinical Science Course, Section 8: External Disease and Cornea. San Francisco: American Academy of Ophthalmology, 2022.
  7. Mannis MJ, Holland EJ. Cornea. Fifth edition. ed: Elsevier Inc., 2022.

Suggested Citation Format

Shonka S, Dotson AD, Greiner MA. Fuchs Endothelial Corneal Dystrophy: From One Medical Student to Another. January 22, 2024; Available from

last updated: 01/22/2024