Fuchs’ Endothelial Dystrophy

From EyeWiki
Original article contributed by: Brandon D. Ayres, MD
All contributors: Alex Kozak, Alpa S. Patel, M.D., Brad H. Feldman, M.D., Brandon D. Ayres, MD, Maria A. Woodward, MD and Penny A. Asbell M.D. M.B.A.
Assigned editor: Brandon D. Ayres, MD
Review: Assigned status Not reviewed by Brandon D. Ayres, MD on February 17, 2017.
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Fuchs’ endothelial dystrophy is a non-inflammatory, sporadic or autosomal dominant, dystrophy involving the endothelial layer of the cornea. With Fuchs’ dystrophy the cornea begins to swell causing glare, halo, and reduced visual acuity. The damage to the cornea in Fuchs’ endothelial dystrophy can be so severe as to cause corneal blindness.

Disease Entity[edit | edit source]

Fuchs' Dystrophy ICD-9 371.57

Disease[edit | edit source]

Fuchs’ endothelial dystrophy is a non-inflammatory, sporadic or autosomal dominant, dystrophy involving the endothelial layer of the cornea. With Fuchs’ dystrophy the cornea begins to swell causing glare, halo, and reduced visual acuity. The damage to the cornea in Fuchs’ endothelial dystrophy can be so severe as to cause corneal blindness.

Etiology[edit | edit source]

Fuchs’ dystrophy is often inherited in an autosomal dominant manner. This means if you have an inherited form of Fuchs’ endothelial dystrophy there is a 50% chance you will pass it on to your children. Spontaneous mutation in the gene for Fuchs’ dystrophy also can cause new Fuchs’ dystrophy in a person with no family history. Currently there are studies underway to try and determine exactly which gene is responsible for the dystrophy, but as of yet we still do not know the exact gene.

Risk Factors[edit | edit source]

The only risk factor for Fuchs’ dystrophy is an affected parent. If you have an affected parent there is at least a 50% chance of passing the gene on to your children. Fuchs’ dystrophy is rarely seen in people younger than 30 to 40 years of age, and seems to present slightly earlier in women.

General Pathology[edit | edit source]

In the early stages of Fuchs’ dystrophy loss of endothelial cells and small excressences of Descemet’s membrane can be seen. These excressences are called “guttata” and look similar to microscopic mushroom caps on the on endothelial surface of the cornea. These guttata are visible on slit lamp exam. The endothelial cells may appear larger than average and may have imbedded pigment. With time fluid from the anterior chamber will collect in the corneal stroma increasing the thickness of the corneal stroma causing reduced vision. With more advanced disease the swelling, or edema, collects in the epithelial layer of the cornea causing small blisters or bullae. With chronic edema fibrotic tissue will form in the subepithelial space and blood vessels and invade the cornea leading to further corneal opacification. Permanent scar tissue eventually will develop in the cornea that will take surgery to remove.

The American Academy of Ophthalmology's Pathology Atlas contains a virtual microscopy image of Fuch’s Endothelial Dystrophy.

Pathophysiology[edit | edit source]

The stroma of the cornea is composed of 78% water. The endothelial cells of the cornea are responsible for maintaining the delicate hydration status of the corneal stroma. Although in early Fuchs’ dystrophy there is enough cellular redundancy to keep the cornea clear, eventually enough cells are damaged so those remaining cannot keep up with the osmotic pressure and fluid begins to collect in the corneal stroma. The excess fluid will eventually migrate to the corneal epithelium causing bullae, which may break. These changes lead to chronic irritation and inflammation causing scar tissue and pannus (or blood vessels) formation.

Primary prevention[edit | edit source]

Fuchs’ dystrophy is an inherited corneal dystrophy affecting the endothelium. There is no primary prevention for this disease entity.

Diagnosis[edit | edit source]

The diagnosis of Fuchs' Endothelial Dystrophy is primary clinical, based on history and slit lamp exam of the eye.

History[edit | edit source]

The classic history for Fuchs’ endothelial dystrophy will be a patient, more commonly a woman, in the fourth to fifth decade of life with symptoms of reduced or fluctuating vision, glare or in some cases recurrent foreign body sensation. Patients often have a family history of a corneal transplantation in one or more family members.

Physical examination[edit | edit source]

Slit lamp exam will vary depending on the severity of the dystrophy. In very mild dystrophy guttata can be seen on the corneal endothelium.
Catfuchs.jpg
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The guttata are often more marked in the central cornea and will be bilateral, though one eye may be more severe than the other. In more advanced Fuchs’ dystrophy a haze will develop in the corneal stroma. As the stroma thickens folds in the Descemet’s membrane and endothelium will be visible. As additional endothelial cells are lost the corneal edema worsens and fluid collects in the epithelium forming microcystic changes as well as large bullae can in the epithelium. The microcysts are often best seen after fluorescein is placed on the cornea leaving areas of negative staining. If a bulla has recently ruptured an epithelial defect may be seen. In more severe, long standing, cases of Fuchs’ dystrophy dense corneal edema and bullous keratopathy are seen. The corneal opacification can be severe enough to prevent visualization of the anterior segment structures as well as the endothelium. The chronic corneal edema will induce sub-epithelial fibrosis as well as corneal vascularization.

Signs[edit | edit source]

The most common signs of Fuchs' Dystrophy include; -Guttata on Descemet's membrane, the guttata tend to be central and slowly become more prominent peripherally -Stromal edema -Endothelial folds -Epithelial microcysts -Epithelial bullae -Sub-epithelial fibrosis -Stromal haze and scar formation -Vascular ingrowth into the cornea

Symptoms[edit | edit source]

Some of the earliest symptoms of Fuchs’ endothelial dystrophy include reduced contrast sensitivity and mild reduction of visual acuity. Patients will often notice glare around a point source of light or have difficulty with nighttime driving. As the dystrophy is often slow in onset, patients may not even notice that their vision is reduced. Once fluid begins to collect in the stroma patients will start to notice fluctuation in vision, typically worse in the early AM and improving toward the end of the day. Vision may be worse on humid or rainy days, and better on dry days. Eventually the diurnal fluctuation reduces and vision becomes reduced all day long. Slowly the vision continues to worsen and eventually intermittent pain can be felt if bullae form and rupture leaving corneal epithelial defects.

Clinical diagnosis[edit | edit source]

The diagnosis of Fuchs’ endothelial dystrophy is clinical. The diagnosis is relatively easy in early disease as you can see the endothelial changes as will as mild corneal stromal edema. In severe cases where you cannot see the endothelium the diagnosis can be more challenging and the diagnosis may need to be based on the contra lateral eye or history.

Diagnostic procedures[edit | edit source]

The diagnosis of Fuchs’ endothelial dystrophy is clinical, however, there are some diagnostic tests that can be helpful. Pachymetry, or measurement of the central corneal thickness, is helpful in following a patient with Fuchs’ dystrophy. Over time you will see increasing corneal thickness as the disease worsens. The rate at which you see increasing corneal thickness can help with counseling patients. The corneal thickness also may help with risk/benefit analysis of any other surgery that may be necessary (such as cataract surgery). Endothelial cell counts can also be helpful when counseling patients as to how quickly their dystrophy may progress as well as how safe any other intraocular surgery may be. In even moderate Fuchs’ dystrophy the cell count can be very difficult to obtain. Evaluation of the endothelium by specular microscopy can demonstrate classic changes of Fuchs' endothelial dystrophy, including guttatta;, variation in cell size and shape and low cell count per unit area.

Laboratory test[edit | edit source]

Fuchs’ endothelial dystrophy is diagnosed clinically. Specular microscopy to visualize the endothelium can corroborate the typical endothelial changes associated with this dystrophy.

Differential diagnosis[edit | edit source]

The differential diagnosis for Fuchs’ endothelial dystrophy includes anything that could induce endothelial deposits and/or corneal swelling. This includes: Pigment dispersion syndrome Keratic precipitates from uveitis Herpetic stromal keratitis Pseudophakic or aphakic bullous keratopathy Iridocorneal endothelial (ICE) dystrophy Congenital hereditary endothelial dystrophy Congenital stromal dystrophy Toxic anterior segment syndrome Posterior Polymorphic Membrane Dystrophy

Management
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General treatment[edit | edit source]

Management of Fuchs’ Dystrophy is purely symptomatic and palliative. At this time there is no treatment that can reverse or halt the progression of Fuchs’ dystrophy.

Medical therapy[edit | edit source]

Medical treatment of Fuchs’ dystrophy begins once patients notice fluctuation in vision. The early treatment is usually in the form of hypertonic saline drops and/or ointments. Use of the hypertonic saline may accelerate the time to visual recovery. Any activity that helps to evaporate fluid off the cornea will help shorten the time to visual recovery, this may include pointing car vents toward the face or blowing air by the eyes using a hair dryer at arms length. Bandage contact lenses can also be quite helpful in management of painful ruptured bullae in more severe disease.

Medical follow up[edit | edit source]

Patients with Fuchs’ dystrophy should be followed depending on the severity of disease. Patients with only mild guttata and minimal to no corneal stromal edema can be followed on an annual basis. More severe patients on maximal medical treatment are followed approximately every 4 months to make sure treatment is adequate. Any patient using a bandage contact lens needs very close follow due to risk for infection.

Surgery[edit | edit source]

As Fuchs’ dystrophy progresses its medical treatment may fail, at that point surgical management becomes necessary. For many years the only option for patients with visually significant Fuchs’ dystrophy was a full thickness corneal transplant or penetrating keratoplasty (PKP). A corneal transplant involves replacement of the full thickness of the cornea in order to replace the endothelial cells. The cornea is held in place with multiple sutures and some sutures may stay in place for several moths to years. Though the surgery is very successful, recovery can be relatively slow sometimes taking a year or more for full visual recovery. The advantage of a full thickness corneal transplant is that it can restore vision even in the most advanced stages of Fuchs’ dystrophy and other necessary intraocular surgery can be performed at the same time as the transplant.
PKP.jpg
Over the past several years there has been a trend to try and treat endothelial dystrophies by transplanting only the posterior, or endothelial, portion of the cornea. Posterior lamellar surgery has been refined over the past several years and now is becoming the standard of care in treatment of early to moderate Fuchs’ endothelial dystrophy. The most popular surgical procedure is currently named Descemet’s Stripping Endothelial Keratoplasty (DSEK) or Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK). The two surgical procedures are to be considered the same in the setting of this discussion. In DSEK only the endothelial layer is removed from the patients’ cornea and replaced by a thin strip of donor corneal stroma with attached, healthy, endothelial cells. This surgery can be performed through a much smaller incision than traditional penetrating keratoplasty. Once the cells are implanted into the eye they are held in place by an air bubble. Using this technique a minimum of corneal sutures are necessary and suture-induced astigmatism is minimized. Once the transplanted cells are in place, the patients’ cornea will be cleared of any excess fluid. Recovery after DSEK is much more rapid than after a full thickness corneal transplant, with patients recovering vision after just a few months. An additional advantage to DSEK is the smaller incision size which keeps the eye much more resistant to damage in the event of ocular trauma.
Dsekair2.jpg
As with full thickness corneal transplants, other necessary intraocular surgery (such as cataract surgery) can be performed at the same time as DSEK, however if the cornea is swollen reducing the ability of the surgeon to see into the eye, the associated surgery can be much more challenging. DSEK seems to be a better option for mild to moderate Fuchs’ dystrophy as once the cornea is scarred from chronic swelling an endothelial transplant may not give satisfactory visual results. In the more advanced cases a full PKP is necessary.

Surgical follow up[edit | edit source]

Follow up is essential after any form of corneal transplantation. Most patients will need to be seen often in the first few weeks after the surgery to ensure surgical success and prevent infection. Routine follow up visits are essential for evaluation of transplant health, wound healing, and visual recovery including removal of sutures minimizing astigmatism. Both full thickness (PKP) and partial thickness (DSEK) transplants have the potential for rejection, just as with any organ transplant. Rejection of the corneal transplant has been seen years after the initial surgery. Follow up is essential in order to prevent and treat rejection if seen.


Complications[edit | edit source]

Surgical complications include infection, poor wound healing, transplant rejection, and suture related complications can be seen in transplant patients.  With a full thickness transplant high refractive error and astigmatism can be seen can also be a problem.  Long term use of topical steroids, necessary to prevent rejection, can induce cataract and glaucoma.  Unique to DSEK includes early onset detachment of the endothelial cells, which may require a repeat air bubble placement, or rarely replacement of endothelial transplant.

Prognosis[edit | edit source]

The prognosis for both penetrating keratoplasty and DSEK is excellent in the patients with Fuchs’ dystrophy. Both procedures will allow for recovery of excellent vision and a normal lifestyle.

Additional Resources[edit | edit source]

http://www.cornealdystrophyfoundation.org

http://www.aao.org/eyesmart/

References[edit | edit source]

External Disease and Cornea, Section 8. Basic and Clinical Science Course, AAO, 2006. Cornea Atlas, 2nd Edition. Krachmer, Palay. Elsevier, 2006. 

Ocular Pathology Atlas. American Academy of Ophthalmology Web site. https://www.aao.org/resident-course/pathology-atlas. Published 2016. Accessed January 4, 2017.  

Weiss JS, Møllwe HU, Lisch W et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008; 27: S1-S42.