PATHOLOGY

Microscopically, the endothelial cells are noted to be more varied in size (polymegethism) and more irregular in shape (pleomorphism) than normal and are disrupted by excrescences of collagen. See the section Scanning in Chapter 2, which includes specular microscopy. Primary dysfunction of the endothelial cells manifests as increased corneal swelling and deposition of collagen and extracellular matrix in the Descemet membrane, which is thickened. There is a reduction in the number of Na⁺,K⁺-ATPase pump sites or in pump function. It is not clear whether the reduction in the posterior nonbanded zone and the increase in thickness of the abnormal posterior collagenous layer are primary effects of endothelial dysfunction or are secondary to chronic corneal edema.

CLINICAL PRESENTATION

Findings vary with the severity of the disease. Cornea guttata is first evident centrally and then spreads toward the periphery (stage 1). In some patients, cornea guttata develops, and the disease never progresses beyond this stage (Fig 7-19). Cornea guttae may become confluent and take on a “beaten metal” appearance. Cornea guttae in late-onset FECD are larger than those seen in early-onset FECD. Stage 2 is characterized by endothelial decompensation and stromal edema (Fig 7-20). As the disease progresses, the Descemet membrane may become thickened, and stromal edema may worsen, causing epithelial bullae and bullous keratopathy (stage 3). The central corneal thickness may approach 1 mm (0.50–0.60 mm is typically considered normal). Subepithelial fibrosis, scarring, and peripheral superficial vascularization secondary to chronic edema occur in end-stage disease (stage 4).

Fuchs dystrophy usually presents in the fourth decade of life or later (except in the case of the early-onset variant, which may present as early as the first decade of life). Symptoms are rare before 50 years of age and are related to the edema, which causes a decrease in vision, contrast sensitivity, and/or glare. Pain may result from ruptured bullae or microcystic edema. Symptoms are often worse upon awakening because of decreased surface evaporation during sleep. Painful episodes may subside once subepithelial fibrosis occurs.

MANAGEMENT

Initial treatment is aimed at reducing corneal edema, which typically begins in the morning, and relieving pain. Use of sodium chloride drops and ointment (5%), as well as measures taken to lower intraocular pressure (IOP), may temporarily help the edema. A bandage contact lens may be useful in treating ruptured bullae. In advanced cases, anterior stromal puncture, placement of amniotic membrane, or a conjunctival flap may be considered to relieve pain, but restoration of vision requires a corneal transplant. In the past, full-thickness (penetrating) keratoplasty was the standard procedure, but this has been largely replaced by endothelial keratoplasty (EK), as the latter targets the pathologic endothelial cells. In one recent case series, removal of a relatively small area of abnormal Descemet membrane and endothelium (descemetorhexis) resulted in mitosis of normal endothelial cells from the periphery, leading to resolution of the edema and improvement in vision. In the future, more traditional keratoplasty may be replaced with descemetorhexis combined with topical and/or intracameral Rho kinase (ROCK) inhibitor to stimulate endothelial proliferation. Another future treatment may be injection of the patient’s own cultured endothelial cells. In advanced cases where there has been anterior corneal scarring, a full-thickness procedure may still be indicated. The prognosis for graft survival is good, especially if the procedure is done before vascularization occurs. See Chapter 15 for detailed discussion of corneal transplantation as well as new therapeutic modalities.

Figure 7-19 Fuchs endothelial corneal dystrophy. Cornea guttae are seen with indirect illumination over the iris and with the red reflex.

(Courtesy of Robert S. Feder, MD.)

Figure 7-20 Fuchs endothelial corneal dystrophy showing the “beaten metal” appearance of the endothelium with mild stromal edema.

(Courtesy of Vincent P. deLuise, MD.)

COMMENT

Specular microscopy may be helpful in the initial evaluation of Fuchs dystrophy and in following the clinical course for loss of corneal endothelial cells; however, it is not necessary in the presence of diffuse confluent guttae. Corneal pachymetry may indicate relative corneal endothelial function, and the readings may change with progression of the disease; pachymetry can also be helpful in determining the relative safety of cataract or other intraocular surgery in a patient with FECD. Endothelial cell counts significantly less than 1000/mm², morning increase in corneal thickness, or the presence of epithelial edema suggests that the cornea may decompensate following intraocular surgery (see Chapter 2); thus, appropriate precautionary measures should be taken. See BCSC Section 11, Lens and Cataract.

Baratz KH, Tosakulwong N, Ryu E, et al. E2-2 protein and Fuchs’s corneal dystrophy. N Engl J Med. 2010;363(11):1016–1024.

Borkar DS, Veldman P, Colby KA. Treatment of Fuchs endothelial dystrophy by Descemet stripping without endothelial keratoplasty. Cornea. 2016;35(10):1267–1273.

Gottsch JD, Sundin OH, Liu SH, et al. Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of Fuchs corneal dystrophy. Invest Ophthalmol Vis Sci. 2005; 46(6):1934–1939.

Li YJ, Minear MA, Rimmler J, et al. Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy. PLoS One [serial online]. 2011; 6(4):e18044. Available at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0018044. Accessed November 20, 2017.

PATHOLOGY

The most distinctive microscopic finding is the appearance of abnormal, multilayered corneal endothelial cells that look and behave like epithelial cells or fibroblasts. These endothelial cells have the following features or characteristics:

• microvilli

• positive immunohistochemical staining for keratin

• rapid and easy growth in cell culture

• intercellular desmosomes

• proliferative tendencies

A diffuse abnormality of Descemet membrane is common, including thickening of the posterior nonbanded layer, a multilaminated appearance, and polymorphous alterations. Similar changes that are not limited to the cornea are seen in iridocorneal endothelial (ICE) syndrome (see Chapter 6). ICE, however, is sporadic and almost always unilateral. Specular microscopy may show typical vesicles and bands, in contrast to the involved cells in ICE syndrome, which appear as dark areas with central highlights and light peripheral borders. Opinion is divided on the value of relying on specular microscopy alone in making the diagnosis. Confocal microscopy reveals vesicular lesions and railroad track, bandlike dark areas with irregular edges.

CLINICAL PRESENTATION

Careful examination of the posterior corneal surface will show any or all of the following:

• isolated grouped endothelial vesicles (Fig 7-21A)

• geographic-shaped, discrete, gray lesions

• broad endothelial bands with scalloped edges (Fig 7-21B)

Various degrees of stromal edema, corectopia, and broad iridocorneal adhesions may also be seen (Fig 7-22). Fine, glasslike iridocorneal adhesions may be seen on gonioscopy. Both angle-closure and open-angle glaucoma can occur, and 14% of patients with PPCD have elevated IOP.

MANAGEMENT

Most patients are asymptomatic. Mild corneal edema may be managed in the same manner as early Fuchs dystrophy. Anterior stromal puncture can be used to induce focal subepithelial fibrosis in cases of localized swelling. With more severe disease, keratoplasty may be required and, if present, glaucoma must be managed. If peripheral anterior synechiae, glaucoma, or both are present preoperatively, the prognosis for successful corneal transplant is reduced. PPCD may recur in the graft. In cases with limited stromal opacification, EK is the preferred approach for targeting the abnormal endothelial cells.

Figure 7-21 Findings in posterior polymorphous corneal dystrophy. A, Broad, oblique view shows clusters of endothelial vesicles, which are commonly seen. B, Scallop-edged endothelial band (arrow).

(Part A courtesy of Robert S. Feder, MD.)

Figure 7-22 Posterior polymorphous corneal dystrophy showing iridocorneal adhesion and corectopia.

Weinstein JE, Weiss JS. Descemet membrane and endothelial dystrophies. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:800–817.