FUCHS’ ENDOTHELIAL CORNEAL DYSTROPHY

Signs and Symptoms

First described by Austrian ophthal-mologist Ernst Fuchs in 1910, the endothelial disorder that bears his name is a bilateral—though often asymmetric—condition, and relatively common in older adults.1,2 While it may occasionally be diagnosed earlier based upon biomicroscopic findings, Fuchs’ dystrophy is rarely symptomatic before 50 years of age. Patients typically present with complaints of diminished vision, foreign body sensation and pain or discomfort, particularly upon awakening.

The key clinical finding is central corneal guttae (historically—though incorrectly—referred to as “guttata”), which represent focal thickenings at the level of Descemet’s membrane. When viewed in direct illumination, guttae appear as gold-colored, hyperreflective bodies on the posterior corneal surface; when retroillumination is used, they resemble small bubbles or holes in the endothelium. Fine endothelial pigment dusting is also commonly seen in association with guttae. In later stages, one may observe stromal edema with folds in Descemet’s membrane, and corneal pannus and bullous keratopathy in severe presentations.

Fuchs’ dystrophy is encountered more commonly and with greater severity in women than men, by a ratio of about 3:1.2 A variety of ocular conditions have been postulated to occur in association with Fuchs’ dystrophy as well, including hypermetropia and shallow anterior chambers, open-angle glaucoma, keratoconus and age-related macular degeneration.3-10 None of these associations has been conclusively proven, however.

Pathophysiology

Fuchs’ dystrophy stems from a primary malfunction of the corneal endothelium, which is likely inherited via an autosomal dominant mechanism with incomplete penetrance.11,12 This leads to widespread loss of endothelial cells and subsequent disruption of the endothelial pump mechanisms, which are responsible for maintaining normal stromal hydration.13 The consequence is an excessive influx of aqueous fluid, leading to corneal stromal edema and a physiologically and optically compromised tissue.

The clinical and histopathological progression of Fuchs’ dystrophy has been well described in numerous prior publications. A clinical staging scheme was proposed many years ago, and is now widely accepted; usually, these stages span a period from 10 to 20 years.2,14,15

Stage 1 is marked by central, irregularly distributed guttae and geographically arranged pigment dusting. Histologically, the endothelial cells show degeneration and deposition of abnormal Descemet’s membrane material. Patients with Stage 1 Fuchs’ are generally asymptomatic.

In Stage 2, patients may begin to experience glare and diminished visual acuity, particularly upon awakening. These symptoms are directly related to coalescence of the guttae with a resultant increase in corneal edema, which can be noted in both the stroma (seen as central corneal thickening) and the epithelium (represented by fine microcysts). As stromal edema increases, folds may be observed in Descemet’s membrane, and vision diminishes accordingly.

Stage 3 of Fuchs’ endothelial dystrophy is heralded by more profound corneal damage in the form of epithelial and subepithelial bullae. The pressure exerted by these lesions on sensitive corneal nerves can induce pain and photophobia, symptoms that can be significantly exacerbated when the bullae rupture.2 Stromal edema is persistent, as is diminished acuity throughout the day.

Permanent corneal scarring occurs in Stage 4, due to the development of subepithelial tissue in the central cornea. Clinically, it appears as an irregular, dense, gray, avascular sheet; histologically, this tissue is composed of active fibroblasts and collagen fibrils sandwiched between the superficial stroma and the epithelium.15 The corneal bullae dissipate at this point, as do the painful episodes experienced by patients. Unfortunately, profound vision loss accompanies the scarring.

Management

Treatment of Fuchs’ endothelial dystrophy varies depending upon the severity of the disease. Patients with early stromal and/or epithelial edema may be treated conservatively with sodium chloride 5% solution throughout the day (e.g., Muro 128 every two to six hours) and sodium chloride 5% ointment overnight. These hypertonic agents serve to diminish corneal edema and improve vision.

Another historical noninvasive measure intended to deturgesce the cornea involves the use of a hair dryer, held at arm’s length and directed toward the eyes.14 Drying the cornea for five to 10 minutes upon waking may improve vision for some time, although caution should be taken not to burn the eye.

As patients become more symptomatic with regard to pain and/or reduced vision, additional treatment options may be employed. Topical nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., Acuvail, Allergan) may be helpful in managing patients with painful bullae; however, the practitioner must understand that these agents merely provide analgesia in cases of Fuchs’ dystrophy. In addition, corneal melts have been associated with the use of certain NSAIDs, and hence these drugs should be used judiciously.16

Historically, ocular hypotensive agents have been advocated for those with Fuchs’ dystrophy, even for those patients in whom intraocular pressure is within normal limits.17 It is hypothesized that by reducing the anterior chamber fluid volume, stress on the endothelial pump mechanisms is decreased, and this subsequently helps to diminish corneal edema; unfortunately, there are no conclusive, prospective studies to support this position to date. Additionally, one class of ocular hypotensives that should specifically be avoided in patients with Fuchs’ dystrophy is the carbonic anhydrase inhibitors (i.e., dorzolamide, brinzolamide, acetazolamide), as these may actually disrupt the endothelial Na-K-ATPase pump.18

Therapeutic (bandage) soft contact lenses may also serve to alleviate patient discomfort in cases of advanced Fuchs’ dystrophy. A flatly fit, high-water content lens helps to mask the irregular astigmatism and diminish pain associated with epithelial bullae.13,17 Silicone hydrogel lenses have also been used in this capacity with some success.19

Despite medical treatment, most patients with Fuchs’ dystrophy will ultimately require surgical intervention.20 Until about 15 years ago, penetrating keratoplasty was the procedure of choice; however, with the advent of deep lamellar keratoplasty, patients now have a surgical option that is less invasive and painful, necessitates a shorter recovery time, and results in fewer instances of rejection.21 In Descemet’s membrane endothelial keratoplasty (DMEK) or Descemet’s stripping endothelial keratoplasty (DSEK)/Descemet’s stripping automated endothelial keratoplasty (DSAEK), only the posterior aspect of the cornea is removed and replaced with donor tissue in an effort to restore a functional endothelial layer.

DMEK may offer better vision and may indeed become the preferred surgical procedure, but currently this extremely thin donor tissue is very fragile and difficult to handle. Consequently, the currently favored surgical technique is DSEK, which selectively peels away approximately 150µm (about 25%) of the posterior stroma, including Descemet’s membrane and the endothelium.22 The donor button of posterior stroma, Descemet’s membrane and endothelium are then implanted.23 DSEK has the advantage of a smaller, potentially self-sealing incision, a smoother recipient interface for the donor tissue and a more rapid rate of visual recovery than penetrating keratoplasty.22

Clinical Pearls

The presence of excessive central guttae in the absence of corneal edema is commonly referred to as endothelial cell dystrophy.13 This condition may remain stable or progress to Fuchs’ dystrophy, which by definition includes some degree of stromal and/or epithelial edema.

Mid-peripheral or peripheral corneal guttae may occasionally be seen in asymptomatic patients over age 40. These entities are known as Hassall-Henle bodies and are of no particular clinical significance.

In place of hypertonic saline, we have experienced modest success with FreshKote (Focus Laboratories) for a variety of corneal disorders. This lubricant uses high colloidal density rather than osmotic pressure from salts to address epithelial edema. It also has the advantage of enhanced lubricity, increased contact time and improved comfort upon instillation.

While topical NSAIDs may be helpful in ameliorating pain associated with Fuchs’ dystrophy, corticosteroids have not been shown to be of significant benefit in this condition.24

1. Eghrari AO, Gottsch JD. Fuchs’ corneal dystrophy. Expert Rev Ophthalmol. 2010;5(2):147-159.

2. Elhalis H, Azizi B, Jurkunas UV. Fuchs endothelial corneal dystrophy. Ocul Surf. 2010;8(4):173-84.

3. Buxton JN, Preston RW, Riechers R, Guilbault N. Tonography in cornea guttata. A preliminary report. Arch Ophthalmol. 1967;77(5):602-3.

4. Pitts JF, Jay JL. The association of Fuchs’s corneal endothelial dystrophy with axial hypermetropia, shallow anterior chamber, and angle closure glaucoma. Br J Ophthalmol. 1990;74(10):601-4.

5. Loewenstein A, Geyer O, Hourvitz D, Lazar M. The association of Fuch’s corneal endothelial dystrophy with angle closure glaucoma. Br J Ophthalmol. 1991;75(8):510.

6. Lipman RM, Rubenstein JB, Torczynski E. Keratoconus and Fuchs’ corneal endothelial dystrophy in a patient and her family. Arch Ophthalmol. 1990;108(7):993-4.

7. Orlin SE, Raber IM, Eagle RC Jr, Scheie HG. Keratoconus associated with corneal endothelial dystrophy. Cornea. 1990;9(4):299-304.

8. Jurkunas U, Azar DT. Potential complications of ocular surgery in patients with coexistent keratoconus and Fuchs’ endothelial dystrophy. Ophthalmology. 2006;113(12):2187-97.

9. Rao GP, Kaye SB, Agius-Fernandez A. Central corneal endothelial guttae and age-related macular degeneration: is there an association? Indian J Ophthalmol. 1998;46(3):145-7.

10. Ali ZK, Whitson JT, Mootha VV, et al. Glaucoma in patients with corneal endothelial dystrophy. Eye Contact Lens. 2011;37(6):332-6.

11. Sundin OH, Jun AS, Broman KW, et al. Linkage of late-onset Fuchs corneal dystrophy to a novel locus at 13pTel-13q12.13. Invest Ophthalmol Vis Sci. 2006;47(1):140-5.

12. Sundin OH, Broman KW, Chang HH, Vito EC, Stark WJ, Gottsch JD. A common locus for late onset Fuchs corneal dystrophy maps to 18q21.2-q21.32. Invest Ophthalmol Vis Sci. 2006;47(9):3919-26.

13. Seitzman GD. Cataract surgery in Fuchs’ dystrophy. Curr Opin Ophthalmol. 2005;16(4):241-5.

14. Adamis AP, Filatov V, Tripathi BJ, Tripathi RC. Fuchs’ endothelial dystrophy of the cornea. Surv Ophthalmol. 1993;38(2):149-68.

15. Waring GO 3rd, Bourne WM, Edelhauser HF, Kenyon KR. The corneal endothelium. Normal and pathologic structure and function. Ophthalmology. 1982;89(6):531-90.

16. Asai T, Nakagami T, Mochizuki M, et al. Three cases of corneal melting after instillation of a new nonsteroidal anti-inflammatory drug. Cornea. 2006;25(2):224-7.

17. Borboli S, Colby K. Mechanisms of disease: Fuchs’ endothelial dystrophy. Ophthalmol Clin North Am. 2002;15(1):17-25.

18. Egan CA, Hodge DO, McLaren JW, Bourne WM. Effect of dorzolamide on corneal endothelial function in normal human eyes. Invest Ophthalmol Vis Sci. 1998;39(1):23-9.

19. Kanpolat A, Ucakhan OO. Therapeutic use of Focus Night & Day contact lenses. Cornea. 2003;22(8):726-34.

20. Afshari NA, Pittard AB, Siddiqui A, Klintworth GK. Clinical study of Fuchs corneal endothelial dystrophy leading to penetrating keratoplasty: a 30-year experience. Arch Ophthalmol. 2006;124(6):777-80.

21. Price MO, Price FW. Descemet’s stripping endothelial keratoplasty. Curr Opin Ophthalmol. 2007;18(4):290-4.

22. Nanavaty MA, Wang X, Shortt AJ. Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy. Cochrane Database Syst Rev. 2014;(2):CD008420.

23. Price FW, Jr, Price MO. Descemet’s stripping with endothelial keratoplasty in 50 eyes: A refractive neutral corneal transplant. J Refract Surg. 2005;21(4):339-45.

24. Wilson SE, Bourne WM, Brubaker RF. Effect of dexamethasone on corneal endothelial function in Fuchs’ dystrophy. Invest Ophthalmol Vis Sci. 1988;29(3):357-61.