Noninfectious Keratitis

Calcific band keratopathy

Seen clinically as a band-shaped calcific plaque in the interpalpebral zone and typically sparing the most peripheral clear cornea, band keratopathy is characterized by the deposition of calcium at the level of the Bowman layer and the anterior stroma. The calcium deposits appear as basophilic granules in H&E sections; the presence of calcium can be further confirmed by the use of special stains such as alizarin red or von Kossa stain (Fig 6-12). Band keratopathy may develop after any chronic local corneal disease, following prolonged chronic inflammation (especially in eyes with a history of chronic juvenile idiopathic arthritis–associated uveitis and in blind, painful eyes), and, less commonly, in association with systemic hypercalcemic states.

Figure 6-12 Calcific band keratopathy. A, Clinical appearance. B, Calcific keratopathy may be treated with epithelial scraping and chelation with ethylenediaminetetraacetic acid (EDTA “scrub”). The calcium is deposited at the level of the Bowman layer (arrows), appearing deeply basophilic (purple) on H&E stain. C, Calcium deposits appear black on von Kossa stain. (Part A

courtesy of Anthony J. Lubniewski, MD; part B courtesy of George J. Harocopos, MD; part C courtesy of Hans E. Grossniklaus, MD.)

Actinic keratopathy

Also known as spheroidal degeneration or Labrador keratopathy, actinic keratopathy involves elastotic degeneration of corneal collagen similar to that seen in pingueculae, pterygia, and solar elastosis of the skin. This condition may be caused by prolonged exposure to solar (actinic) irradiation. It may also be caused by corneal inflammation, sometimes in association with calcific band keratopathy. The actinic damage usually occurs within the interpalpebral fissure. Clinical examination discloses translucent, golden-brown spheroidal deposits in the superficial cornea (Fig 6- 13A). H&E-stained sections show basophilic globules beneath the epithelium in the region of the Bowman layer and the anterior stroma (Fig 6-13B). The deposits stain black with special stains for

elastin, such as the Verhoeff–van Gieson (VVG) stain.

Figure 6-13 Actinic keratopathy (spheroidal degeneration). A, Gross appearance of corneal button. The air bubbles are artifacts. B, Histology shows lightly staining basophilic globules (arrows) in the epithelium and superficial stroma. (Courtesy of

Hans E. Grossniklaus, MD.)

Pannus

Pannus refers to the growth of fibrovascular or fibrous tissue between the epithelium and the Bowman layer (Fig 6-14). The Bowman layer may be disrupted. Pannus is frequently seen in cases of chronic corneal edema or following prolonged corneal inflammation.

Figure 6-14 Fibrovascular pannus. A, Clinical appearance on the superior cornea. B, Fibrovascular pannus (between arrows) is interposed between the epithelium and the Bowman layer. (Part A courtesy of George J. Harocopos, MD.)

Bullous keratopathy

Intraocular surgery, most commonly cataract surgery, invariably results in some loss of corneal endothelial cells. In cases of extensive endothelial cell loss, the cornea may decompensate postoperatively, either early in the postoperative period or years later, after more endothelial cells are lost with age. When the endothelium begins to decompensate, Descemet folds and stromal edema occur, followed by intracellular epithelial edema and, ultimately, separation of the epithelium from the Bowman layer. Small separations are referred to as “microcysts”; these may coalesce to form large separations, known as bullae. In more advanced cases of bullous keratopathy, as in Fuchs endothelial dystrophy (discussed later), secondary epithelial basement membrane changes and fibrous

pannus may be seen. The Descemet membrane may be thickened, but it typically does not show guttae (Fig 6-15). Although bullous keratopathy is more commonly seen after cataract surgery, in which case it is termed pseudophakic or aphakic bullous keratopathy, it may also be seen after other forms of intraocular surgery, for example, multiple glaucoma procedures or retinal detachment repair with silicone oil (“silicone oil keratopathy”).

Figure 6-15 Pseudophakic bullous keratopathy. A, Clinical appearance of severe bullous keratopathy associated with an anterior chamber lens implant. B, Corneal button from penetrating keratoplasty. Note the subepithelial bullae (arrows). Also note diffuse endothelial cell loss, without guttae of Descemet membrane. (Part A courtesy of Andrew J.W. Huang, MD; part B courtesy of

George J. Harocopos, MD.)

Corneal graft failure

Failure of an existing corneal graft is one of the most common indications for penetrating keratoplasty. The final common pathway of graft failure is endothelial cell loss. The endothelial cells of a graft may gradually decrease over time until failure occurs, or there may be an acute event resulting in endothelial cell loss, such as a rejection episode or ulcerative keratitis. When endothelial failure occurs, there is often associated bullous keratopathy. In about half of cases, a fibrous retrocorneal membrane is visualized (Fig 6-16). If the membrane is thick and contiguous with the corneal stroma in the region of an incision, then the membrane may be termed fibrous downgrowth or ingrowth. Less commonly, a graft may fail because of growth of surface epithelium through a poorly apposed wound and onto the retrocorneal surface, that is, epithelial downgrowth or ingrowth. The main risk factor for fibrous or epithelial downgrowth is multiple prior penetrating keratoplasties. Both types of downgrowth are very poor prognostic signs for graft survival and for general ocular health, as they are typically associated with secondary angle-closure glaucoma.

Figure 6-16 Corneal graft failure. A, PAS stain of corneal button, showing diffuse endothelial cell loss and fibrous retrocorneal membrane (F). There is secondary bullous keratopathy (arrowhead) and epithelial basement membrane thickening/redundancy (arrow). B, Clinical appearance of fibrous downgrowth (arrows). C, PAS stain of corneal button (different patient) showing fibrous downgrowth (FD). The continuity between the fibrous downgrowth and the corneal stroma may be seen through the break in Descemet membrane (arrow) at the graft–host interface. Also note peripheral anterior synechiae, with iris tissue (I) adherent to the fibrous membrane. D, Clinical appearance of epithelial downgrowth (arrowheads). E, Histology of failed graft (different patient) with epithelial downgrowth (arrowhead) and diffuse endothelial cell loss. Also note secondary bullous keratopathy, with ruptured bulla (arrows). (Parts A, C, and E courtesy of George J. Harocopos, MD;

parts B and D courtesy of Anthony J. Lubniewski, MD.)

Keratoconus

Keratoconus is a bilateral noninflammatory condition characterized by central or inferocentral ectasia of the cornea, typically diagnosed during adolescence or young adulthood (Fig 6-17A). It is often sporadic, but family history is positive in some cases, thereby blurring the distinction between degeneration and dystrophy in this condition. Keratoconus can occur as an isolated finding, or it may be associated with other ocular disorders or with systemic conditions, including atopy, Down syndrome, and Marfan syndrome. The alteration in the normal corneal contour produces myopia and

irregular astigmatism. In advanced disease, visually significant apical scarring develops, often requiring therapeutic keratoplasty. A small percentage of keratoconus patients develop a spontaneous break in Descemet membrane, resulting in acute corneal edema known as corneal hydrops.

Histologic findings in keratoconus include central stromal thinning and focal discontinuities in the Bowman layer. Apical anterior stromal fibrosis is often present (Fig 6-17B, C). Iron deposition in the basal epithelial layers at the base of the cone (Fleischer ring) can sometimes be demonstrated with Prussian blue stain (Fig 6-17D). In patients with a history of hydrops, a break in Descemet membrane may be observed (Fig 6-17E). Occasionally, amyloid material may accumulate in the anterior cornea in advanced keratoconus (an example of secondary localized amyloidosis).

Pellucid marginal degeneration is another ectatic disorder and is likely part of the same disease spectrum as keratoconus. The stromal thinning of pellucid marginal degeneration is typically more inferior than that of keratoconus.

and may also be found extracellularly on the posterior corneal surface (Fig 6-18). In pigment dispersion syndrome, melanin pigment is also seen in and around the endothelial cells lining the trabecular meshwork, correlating with the abnormally dark color of the meshwork observed gonioscopically (see Chapter 7, Fig 7-13). See also BCSC Section 10, Glaucoma.

Blood staining of the cornea may complicate hyphema when the intraocular pressure (IOP) is very high for a long duration; however, if the endothelium is compromised, blood staining can occur even at normal or low IOP (Fig 6-19). Histologically, red blood cells and their breakdown products (mostly hemoglobin and also small amounts of hemosiderin) are seen in the corneal stroma. The hemosiderin is located in the cytoplasm of keratocytes and may be demonstrated with iron stains such as Prussian blue.

Iron deposition in the corneal epithelium in keratoconus (Fleischer ring) was previously discussed (Fig 6-17D).

See BCSC Section 8, External Disease and Cornea, for additional discussion of blood staining of the cornea as well as other forms of ocular surface iron lines.

Figure 6-18 Krukenberg spindle. A, Clinical appearance of Krukenberg spindle (arrow). B, Melanin pigment is found within the

cytoplasm of endothelial cells (arrows). (Part A courtesy of L.J. Katz, MD; part B courtesy of Debra J. Shetlar, MD.)