Fuchs’ Endothelial Dystrophy

From EyeWiki


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.

Fuchs' endothelial dystrophy


Disease Entity

Fuchs' Dystrophy ICD-9 371.57

Disease

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, halos, and reduced visual acuity. The damage to the cornea in Fuchs’ endothelial dystrophy can be so severe as to cause corneal blindness.

Etiology

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

The only risk factor for Fuchs’ dystrophy is an affected parent. Affected individuals have at least a 50% chance of passing the gene on to their 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

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 embedded 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 called bullae. With chronic edema, fibrotic tissue will form in the subepithelial space and invade the cornea leading to further corneal opacification. Permanent scar tissue eventually will develop in the cornea that will require surgery to remove.

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

Pathophysiology

The stroma of the cornea is composed of 78% water. The endothelial cells of the cornea are responsible for maintaining the delicate hydration status (78% water) of the corneal stroma. Although in early Fuchs’ dystrophy there are enough healthy endothelial cells to prevent the cornea from becoming too saturated with extra water, eventually enough cells are damaged and those remaining cannot keep up with the osmotic pressure. At this point, fluid begins to collect in the corneal stroma which can result in blurry vision. The excess fluid will eventually migrate to the corneal epithelium causing bullae, which may break and cause pain and/or create a risk for infection within open surface wounds. These changes lead to chronic irritation and inflammation causing scar tissue and possible pannus (or blood vessels) formation.

Primary prevention

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

Diagnosis

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

History

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

Slit lamp exam will vary depending on the severity of the dystrophy.

In very mild dystrophy, guttata can be seen on the corneal endothelium.
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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 epithelial bullae . Microcysts are 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

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

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 vision stops fluctuations and becomes constantly blurry. Slowly the vision continues to worsen and eventually intermittent pain can be felt if bullae form and rupture leaving corneal epithelial defects.

Clinical diagnosis

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 contralateral eye or by history.

Diagnostic procedures

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

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

Differential diagnosis

The differential diagnosis for Fuchs’ endothelial dystrophy includes anything that could induce endothelial deposits and/or corneal swelling:

  • 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

Medical therapy

Medical treatment of Fuchs’ dystrophy begins once patients notice fluctuations in vision. The early treatment is usually in the form of hypertonic saline (such as Muro 128 or sodium chloride) eye drops and/or ointments. Use of the hypertonic saline may stabilize or improve vision by drawing extra water out of the cornea. Any activity that helps to evaporate fluid off the cornea will help shorten the time to visual recovery. Such activities may include pointing car vents toward the face or blowing air by the eyes using a hair dryer at arm's length. Bandage contact lenses can also be quite helpful in management of painful ruptured bullae in more severe disease.

Medical follow up

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 may be followed every 6-12 months. Patients with more severe disease, on maximal medical treatment, might be followed more closely to make sure treatment is adequate. Any patient using a bandage contact lens needs very close follow-up due to the risk of infection.

Surgery

As Fuchs’ dystrophy progresses, medical treatment may fail and surgical management becomes necessary.

Penetrating keratoplasty (PKP or PK):

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 (as shown in the diagram on the right with 17 sutures) and some sutures may stay in place for several months or even years. Though the surgery is very successful, recovery can be relatively slow, sometimes taking a year or more for full visual recovery. It may take a year or longer for vision to stabilize and strong glasses or specialty fit contact lenses are often required to achieve the best vision after surgery. Patients may need to administer steroid eye drops (and be monitored while on these drops) for many years to prevent rejection of the cornea graft. The advantage of a full thickness corneal transplant is that it can restore vision even in the most advanced stages of Fuchs’ dystrophy.
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Descemet's Stripping Endothelial Keratoplasty (DSEK):

Since the early 2000s, 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 (also referred to as endothelial keratoplasty) is now the standard of care in treatment of early to moderate Fuchs’ endothelial dystrophy. The most common type of DSEK performed in the US is sometimes referred to as Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK).

In DSEK, only the endothelial layer is removed from the affected cornea and replaced by a thin strip of donor posterior corneal stroma with attached Descemet's membrane and healthy endothelial cells. This surgery can be performed through a much smaller incision than traditional penetrating keratoplasty. Once the donor tissue is implanted into the eye, it is temporarily held in place by an air bubble (photo below). The air bubble usually dissolves over a couple of days. For the first day, the patient must remain in the supine (face up) position in order to keep the bubble centered and help the graft attach. (Exact instructions regarding position vary from surgeon to surgeon.) The new, transplanted endothelial cells pump excess water out of the cornea and restore cornea clarity resulting in the restoration of better quality vision.
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Using this technique, only a few (or sometimes no) sutures are required and suture-induced astigmatism is less significant than with PKP. This results in better quality postoperative vision without glasses. Although glasses are still often required after DSEK, the prescription tends to be much less strong compared to post-PKP prescriptions. DSEK patients also recover vision more quickly than PKP patients.

The smaller DSEK wound results in fewer wound leaks, less chance of postoperative infection, and greater stability of the eye. Compared to eyes with PKP, eyes with DSEK are more resistant to damage in the unfortunate event of ocular trauma.

As with full thickness corneal transplants, other necessary intra-ocular surgery (such as cataract surgery) can sometimes be performed at the same time as DSEK.

DSEK is a better option for mild to moderate Fuchs’ dystrophy. Once the cornea is scarred from chronic swelling an endothelial transplant may not give satisfactory visual results. In these more advanced Fuchs' cases, a full PKP may be necessary.

Please visit the eyewiki DSEK page (https://eyewiki.aao.org/Descemet_Stripping_Endothelial_Keratoplasty) for more information.

Descemet's Membrane Endothelial Keratoplasty (DMEK):

The next iteration of corneal transplant surgery is called DMEK. Developed in 2006 by Dr Gerrit Melles, this elegant procedure transplants an even thinner sliver of tissue consisting only of Descemet's membrane and endothelial cells (without any corneal stroma). The procedure is similar to DSEK; however, a different surgical technique is used to handle this very delicate tissue and deliver it into the eye and place it in the correct position. Similar to DSEK, an air (or sometime gas) bubble is placed in the eye to help the transplanted tissue attach and the patient must remain in the supine (face up) position for 1-3 days following surgery. (Exact positioning instructions vary from surgeon to surgeon.) Because the tissue is thinner than DSEK tissue, it can be more challenging to attach and the need for longer periods of supine positioning or possible "re-bubbling" procedures is higher with DMEK compared to DSEK. However, the thinner tissue with DMEK also translates into better quality vision for many patients.

Please visit the eyewiki DMEK page (https://eyewiki.org/Descemet_Membrane_Endothelial_Keratoplasty) for more information.

Descemetorhexis Without Endothelial Keratoplasty (DWEK)

Also sometimes referred to as Descemet's Stripping Only (DSO), DWEK is the latest surgical option for some patients with Fuchs'. Select Fuchs' patients with guttae localized in the central cornea and with a fairly healthy peripheral endothelium are candidates for the procedure. During DWEK, the ophthalmologist carefully strips away a 4mm circle of central diseased endothelial cells without placing any donor cornea tissue. If the surgery succeeds, healthy endothelial cells from the intact periphery will migrate centrally, covering the defect, and providing good quality vision. The surgery can be abetted by prescribing a rho kinase inhibitor eye drop for the patient to use post-operatively. (Note that the use of this drop in this setting does not currently have FDA approval in the US.) The potential benefits of this surgery include a very small wound, no need for post-operative supine positioning of the patient, no concern for rejection of transplanted tissue (since no tissue is implanted), and no need for long term monitoring while on steroid drops (usually used for many months or years to prevent rejection of transplanted cornea tissue in PK, DSEK, and DMEK). One main drawback of the surgery is that the central cornea will swell up right after surgery and the vision will become temporarily worse. The other drawback is that DWEK is not successful in all cases and some patients will endure worse vision for awhile and then go on to require DMEK or DSEK.

Please visit the eyewiki DWEK page (https://eyewiki.aao.org/Descemetorhexis_Without_Endothelial_Keratoplasty) for more information.

Surgical follow up

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 monitor for infection. Routine follow-up visits are essential for evaluation of transplant health, wound healing, and visual recovery including removal of sutures minimizing astigmatism. PKP, DSEK, and DMEK transplants have the potential for rejection, just as with any organ transplant. Rejection of the corneal transplant can occur at any point after surgery. Follow-up is essential in order to prevent and treat rejection if seen. Follow-up is also necessary to monitor for glaucoma, a possible side effect of long term steroid drops used to prevent rejection. Glaucoma can cause permanent vision loss in some transplant patients.

Complications

Surgical complications include infection, bleeding, wound leaks, transplant rejection, and suture related complications.  With a full thickness transplant high refractive error and astigmatism can also be a problem.  Long term use of topical steroids, necessary to prevent rejection, can induce cataract and glaucoma.  DSEK and DMEK surgeries have risks of detachment of the graft with the consequent need for re-bubbling and repeat supine positioning and, occasionally, exchange of a graft that isn't attaching for a new graft. Complications can be associated with pain or loss of vision and can lead to the need for additional procedures and office visits.

Prognosis

The prognosis for patients with Fuchs' is excellent. The various surgical treatments available today have very good success rates.

Additional Resources

References

  1. External Disease and Cornea, Section 8. Basic and Clinical Science Course, AAO, 2006. Cornea Atlas, 2nd Edition. Krachmer, Palay. Elsevier, 2006. 
  2. Ocular Pathology Atlas. American Academy of Ophthalmology Web site. https://www.aao.org/resident-course/pathology-atlas. Published 2016. Accessed January 4, 2017.  
  3. Weiss JS, Møllwe HU, Lisch W et al. The IC3D Classification of the Corneal Dystrophies. Cornea. 2008; 27: S1-S42.