Stromal Degenerations
White limbal girdle of Vogt
Two forms of the white limbal girdle of Vogt have been described. Type I is a narrow, concentric, whitish superficial band running along the limbus in the palpebral fissure and is generally thought to represent early calcific band keratopathy. A lucid interval appears between the limbus and the girdle. This girdle is a degenerative change of the anterior limiting membrane, with chalklike opacities and small clear areas resembling the holes in Swiss cheese. Type II consists of small, white, flecklike, and needlelike deposits that are often seen at the nasal and temporal limbus in older patients. No clear interval separates this girdle from the limbus (Fig 6-8). Histologically, there is epithelial elastotic degeneration of collagen, sometimes with particles of calcium.
Corneal arcus
Corneal arcus, or arcus senilis, is most often an involutional change that is modified by genetic factors and caused by the deposition of lipid in the peripheral corneal stroma. Arcus starts at the inferior and superior poles of the cornea and, in the late stages, involves the entire circumference. The prevalence of corneal arcus is higher in African Americans and males. The arcus has a hazy white appearance, a sharp outer border, and an indistinct central border; it is denser superiorly and inferiorly (Fig 6-9). A lucid interval is usually present between the peripheral edge of the arcus and the limbus. The lipid is found to be concentrated mainly in 2 areas of the peripheral corneal stroma: one adjacent to the Bowman layer and another near the Descemet membrane.
In patients younger than 40 years, the presence of arcus may be indicative of a hyperlipoproteinemia (involving low-density lipoproteins) with elevated serum cholesterol level (see Chapter 8). Corneal arcus may also occur as a congenital anomaly (arcus juvenilis).
Unilateral corneal arcus is a rare condition associated with contralateral carotid artery disease or ocular hypotony. Arcus is also seen in Schnyder corneal dystrophy and osteogenesis imperfecta.
Crocodile shagreen
Anterior crocodile shagreen, or mosaic degeneration, is a bilateral, usually visually insignificant condition with a characteristic mosaic pattern. It consists of centrally located polygonal, gray opacities at the level of the Bowman layer that are separated by clear zones. Histologically, the Bowman layer is indented, forming ridges, and may be calcified. In posterior crocodile shagreen, there are similar changes in the deep stroma, near the Descemet membrane.
Cornea farinata
Cornea farinata is an involutional change, most likely dominantly transmitted, in which the deep corneal stroma shows many subtle dotlike and comma-shaped opacities (Fig 6-10). These opacities are often best seen in retroillumination. The opacities in pre-Descemet corneal dystrophy are similar but larger and more polymorphous. Confocal microscopy reveals highly reflective particles in the cytoplasm of keratocytes in the deep stroma, adjacent to the corneal endothelial layer. No abnormalities are detected in the epithelial layer, in the mid-stromal layer, at the level of the Descemet membrane, or in the endothelial layer. The deposits may consist of lipofuscin, a degenerative pigment that appears in some aging cells. The condition does not affect vision and has no clinical significance, except that it is sometimes mistaken for a progressive dystrophy.
Polymorphic amyloid degeneration
Polymorphic amyloid degeneration is a bilaterally symmetric, primarily axial, and slowly progressive corneal degeneration that appears late in life and is characterized by amyloid deposition. The deposits, which can resemble some of those seen in early lattice corneal dystrophy type 3, form corneal opacities, appearing as stellate flecks in mid- to deep stroma and as irregular filaments. The opacities are gray to white and somewhat refractile, but they appear translucent in retroillumination (Fig 6-11). The intervening stroma appears clear, and vision is usually normal. There is also an acquired (secondary localized) corneal amyloidosis; see Chapter 8 for a discussion of the amyloidoses.
Senile furrow degeneration
Senile furrow degeneration is seen in older patients with corneal arcus and refers to an appearance of peripheral thinning in the lucid interval of the arcus (see the section “Corneal arcus,” earlier in this chapter). Although slight thinning is occasionally present, it is usually more apparent than real. True thinning can eventually occur in the affected area and should be considered by the cataract surgeon, particularly with placement of the clear corneal incision, because of the risk of wound leak. The corneal epithelium is intact. There is no inflammation, vascularization, or potential for perforation. Vision is rarely affected, and no treatment is required.
Terrien marginal degeneration
Terrien marginal degeneration is a noninflammatory, slowly progressive thinning of the peripheral cornea. It is usually bilateral but can be very asymmetric. Although individuals of any age can be affected, this degeneration appears primarily in those older than 40 years. Males and females are affected equally, with men affected slightly more frequently. The cause of this condition is unknown. Initially presenting in the superonasal area, the thinning spreads circumferentially; in rare cases, it involves the central cornea or inferior limbus. Affected patients are usually asymptomatic until the thinning results in increased astigmatism and subsequent reduction in vision.
The corneal epithelium remains intact, and a fine pannus traverses the area of stromal thinning. A line of lipid deposits appears at the leading edge of the pannus (central edge of the furrow) (Fig 6-12). Spontaneous perforation is rare, although it can easily occur with minor trauma. Ruptures in the Descemet membrane can result in acute corneal hydrops or even a corneal cyst. Corneal topography reveals flattening of the peripheral thinned cornea, with steepening of the corneal surface approximately 90° away from the midpoint of the thinned area. This pattern usually results in high against-the-rule or oblique astigmatism.
An inflammatory condition of the peripheral cornea that may resemble Terrien marginal degeneration occurs in rare instances in children and young adults and is also known as Fuchs superficial marginal keratitis. This condition may represent different clinical features of the same disease process.
Surgical correction is indicated when perforation is imminent because of progressive thinning, or when marked astigmatism significantly limits vision. Crescent-shaped lamellar or full-thickness corneoscleral patch grafts may be used; they have been reported to arrest the progression of severe against-the-rule astigmatism for up to 20 years. Annular lamellar keratoplasty grafts may be required in severe cases of 360° marginal degeneration.
Chan AT, Ulate R, Goldich Y, Rootman DS, Chan CC. Terrien marginal degeneration: clinical characteristics and outcomes. Am J Ophthalmol. 2015;160(5):867–872.e1.
Keenan JD, Mandel MR, Margolis TP. Peripheral ulcerative keratitis associated with vasculitis manifesting asymmetrically as Fuchs superficial marginal keratitis and Terrien marginal degeneration. Cornea. 2011;30(7):825–827.
Salzmann nodular degeneration
Salzmann nodular degeneration is a noninflammatory corneal degeneration that sometimes occurs as a late sequela to long-standing keratitis such as phlyctenulosis, trachoma, and interstitial keratitis; it may also be idiopathic. The degeneration may not appear until years after the active keratitis has subsided. It can be bilateral and is more common in middle-aged and older women. The nodules are gray-white or blue-white and elevated (Fig 6-13). They often develop in a roughly circular configuration in the central or paracentral cornea and at the ends of vessels of a pannus.
Histologic examination reveals localized replacement of the Bowman layer with hyaline and fibrillar material, probably representing basement membrane and material similar to that found in spheroidal degeneration (discussed earlier). Confocal microscopy reveals elongated basal epithelial cells and activated keratocytes in the anterior stroma, near the nodules; occasionally, subbasal nerves and tortuous stromal nerve bundles are also seen.
Treatment for mild cases is ocular lubrication; manual superficial keratectomy may be indicated in more severe cases (those causing decreased vision secondary to irregular astigmatism). This degeneration may recur after removal of the nodules.
A variant of Salzmann nodular degeneration, called peripheral hypertrophic subepithelial corneal degeneration, has been described. It is most common in women. Bilateral, fairly symmetric, peripheral, and hypertrophic subepithelial corneal opacification is present. Adjacent superficial limbal vascularization with occasional pseudopterygium has been noted (Fig 6-14). Underlying chronic ocular surface inflammation is absent, and minimal relief of ocular irritation is achieved with topical corticosteroids.
Gore DM, Iovieno A, Connell BJ, Alexander R, Meligonis G, Dart JK. Peripheral hypertrophic subepithelial corneal degeneration: nomenclature, phenotypes, and long-term outcomes. Ophthalmology. 2013;120(5):892–898.
Roszkowska AM, Aragona P, Spinella R, Pisani A, Puzzolo D, Micali A. Morphologic and confocal investigation on Salzmann nodular degeneration of the cornea. Invest Ophthalmol Vis Sci. 2011;52(8):5910–5919.
Corneal keloid
Corneal keloids are superficial, sometimes protuberant, glistening, white corneal masses that can eventually involve the entire corneal surface. They are thought to be secondary to a vigorous fibrotic response to corneal injury or chronic ocular surface inflammation. Keloids can be congenital or primary, and they have been reported in association with many congenital conditions, such as Lowe disease (oculocerebrorenal syndrome). They have sometimes been confused with hypertrophic scars, Salzmann degeneration, or dermoids. Treatment of symptomatic patients may include superficial keratectomy or penetrating or lamellar keratoplasty.
Bakhtiari P, Agarwal DR, Fernandez AA, et al. Corneal keloid: report of natural history and outcome of surgical management in two cases. Cornea. 2013;32(12):1621–1624.
Lipid keratopathy
In lipid keratopathy, yellow or cream-colored lipids containing cholesterol, neutral fats, and glycoproteins are deposited in the superficial or deeper cornea, usually after prolonged corneal inflammation with scarring and corneal vascularization (eg, herpes simplex or herpes zoster keratitis, interstitial keratitis, including syphilitic). This form is best described as secondary lipid keratopathy (Fig 6-15). In rare instances, lipid keratopathy has been reported with no evidence of an antecedent infection, inflammatory process, or corneal damage. These cases are best described as primary lipid keratopathy. Treatment is indicated in cases of decreased vision or compromised cosmetic appearance. Lipid keratopathy should be distinguished from Schnyder corneal dystrophy, a rare autosomal dominant stromal dystrophy characterized by bilateral corneal opacification resulting from an abnormal accumulation of cholesterol and lipid. Controlling the neovascularization with topical corticosteroids may reduce or even stop progression of the keratopathy. Argon laser treatment with and without fluorescein, photodynamic therapy with verteporfin, and subconjunctival and topical bevacizumab have been reported to reduce corneal neovascularization and lipid deposition.
Chang JH, Garg NK, Lunde E, Han KY, Jain S, Azar DT. Corneal neovascularization: an anti-VEGF therapy review. Surv Ophthalmol. 2012;57(5):415–429.
Goh YW, McGhee CN, Patel DV, Barnes R, Misra S. Treatment of herpes zoster–related corneal neovascularization and lipid keratopathy by photodynamic therapy. Clin Exp Optom. 2014;97(3):274–277.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.