Chapter 60 – Conjunctival and Corneal Degenerations
QAIS A. FARJO
• Secondary deterioration or deposition in the cornea and/or conjunctiva, distinct from the dystrophies.
• Bilateral usually.
• Typically does not affect vision.
• Increased prevalence with age.
• Often associated with chronic light exposure.
• May follow past inflammation.
• Not inherited.
Degenerations of the cornea and conjunctiva are common conditions that have, in most cases, relatively little effect on ocular function and vision. These conditions increase in prevalence with increasing age—as a result of past inflammation, of long-term toxic effects of environmental exposure, or of aging itself. Unlike corneal dystrophies, corneal degenerations are not inherited, may be unilateral or bilateral, and are often associated with corneal vascularization. Degenerations tend to involve the peripheral cornea and may overlap the limbus and conjunctiva. Conjunctival degenerations are discussed first, followed by those that involve the cornea.
Pingueculae are areas of bulbar conjunctival thickening that adjoin the limbus in the palpebral fissure area ( Fig. 60-1 ). They are elevated, white to yellow in color, and horizontally oriented. Also, they are less transparent than normal conjunctiva, often have a fatty appearance, are usually bilateral, and are located nasally more often than temporally. When a pinguecula crosses the limbus onto the cornea, it is called a pterygium. Current information, however, suggests that pinguecula does not progress to pterygium and that the two are distinct disorders.
The causes of pingueculae are not known with certainty. Good evidence exists, however, of an association with increasing age and ultraviolet light exposure. Pingueculae are seen in most eyes by 70 years of age and in almost all by 80 years of age.  Chronic sunlight exposure has been found to be a factor by association with outdoor work and equatorial residence. In some studies, the strength of this association is less than that for pterygium. The association with light exposure has also been found
Figure 60-1 Nasal pinguecula. Elevated conjunctival lesion encroaches on nasal limbus.
in welders, for whom a higher rate of pingueculae occurs than for nonwelders as well as an increasing rate with increasing welding exposure. It is thought that the predominantly nasal location is related to reflection of light from the nose onto the nasal conjunctiva. The effect of ultraviolet light may be mediated by mutations in the p53 gene.
Pingueculae are associated only rarely with any symptoms other than a minimal cosmetic defect. They may become red with surface keratinization. When inflamed, the diagnosis of pingueculitis may be given.
Distinguishing pingueculae from other lesions is usually not a problem because of the typical appearance. Conjunctival intraepithelial neoplasia may be difficult to differentiate from keratinization of a pinguecula. Gaucher’s disease type I is said to be associated with tan pingueculae, but this is probably not a specific finding.
The histopathology of pingueculae is characterized by elastotic degeneration with hyalinization of the conjunctival stroma, collection of basophilic elastotic fibers, and granular deposits.
Pingueculitis responds to a brief course of topical corticosteroids or nonsteroidal anti-inflammatory agents. Chronically inflamed or cosmetically unsatisfactory pingueculae rarely warrant simple excision.
Pterygium is a growth onto the cornea, usually nasally, of fibrovascular tissue that is continuous with the conjunctiva. It occurs in the palpebral fissure area, more often nasally than temporally, although either or both (“double” pterygium) occur ( Fig. 60-2 ). Like pinguecula, it is a degenerative lesion, although it
Figure 60-2 Double pterygium. A, Note both nasal and temporal pterygia in a 57-year-old farmer. B, It is the invasion of the cornea that distinguishes a pterygium from a pinguecula.
may appear similar to pseudopterygium, which is a conjunctival adhesion to the cornea secondary to previous trauma or inflammation such as peripheral corneal ulceration. A pseudopterygium often has an atypical position and is not adherent at all points, so a probe can be passed beneath it peripherally.
Like pinguecula, pterygium is associated with ultraviolet light exposure. It occurs at highest prevalence and most severely in tropical areas near the equator and to a lesser and milder degree in cooler climates.  Both blue and ultraviolet light have been implicated in its causation, as demonstrated in watermen. Outdoor work in situations with high light reflectivity, including from sand and water, enhances pterygium development, and the use of hats and sunglasses is protective. In the past, the pathogenesis of pterygium was thought to be related to disturbance of the tear film spread central to a pinguecula. New theories include the possibility of damage to limbal stem cells by ultraviolet light and by activation of matrix metalloproteinases.   The histopathology of pterygium is similar to that of pinguecula except that Bowman’s membrane is destroyed within the corneal component.
Pterygia warrant treatment when they encroach upon the visual axis, induce significant regular or irregular astigmatism, or become cosmetically bothersome. A variety of surgical techniques have been developed. Most methods for small primary pterygia involve simple excision of the pterygium on the cornea and sclera. For larger and recurrent pterygia, the goal of treatment has been prevention of recurrence. The recurrence rates after older techniques have been very high: 50% reoccur within 4 months of excision and nearly all within 1 year. Beta radiation applied postoperatively to the pterygium base was popular for many years and is moderately effective. It is now used less because
Figure 60-3 Senile scleral plaque. Calcium deposition appears as a gray scleral plaque under the medial rectus muscle insertion.
of reports of late scleral necrosis. Currently, the most widely used techniques are conjunctival autografting and mitomycin C application. These methods are equally effective. Topical mitomycin C applied at the time of surgery appears to be relatively safe  and to decrease the potential toxicity of postoperative applications, although scleral and corneal melting may still occur. Human amniotic membrane grafts have also been shown to be effective.
Senile Scleral Plaques
Senile scleral plaques occur in the sclera rather than the cornea or conjunctiva, but they are frequently misinterpreted as a melting process similar to that of corneal degenerations or as conjunctival depositions. These lesions appear as yellow, gray, or black vertical bands just anterior to the insertion of the medial and lateral rectus muscles in elderly patients ( Fig. 60-3 ). They become more common after the age of 60 years and, like pinguecula and pterygium, may be related to ultraviolet light exposure. Histologically, calcium deposits along with decreased cellularity and hyalinization are seen. These lesions do not need therapy.
See later under Corneal Degenerations.
No adequate system exists by which to categorize logically all corneal degenerations, as this is a diverse group of conditions. The conditions that occur in the corneal periphery are discussed first, followed by the conditions that occur more centrally. This is an arbitrary division as many conditions, such as spheroidal degeneration or band keratopathy, can be found in either or both locations.
Corneal Arcus (Arcus Senilis)
Corneal arcus is the deposition in the corneal periphery of a gray to white or occasionally yellow band of opacity. It comprises fine dots and has a clear zone between it and the limbus, about 0.3?mm wide, known as the clear interval of Vogt. Arcus usually has a diffuse central border and a sharper peripheral border ( Fig. 60-4 ). It begins superiorly and inferiorly, possibly because of increased corneal temperature in unexposed areas, and gradually spreads to involve the entire corneal periphery but becomes densest and widest above. The deposits occur in the deep stroma initially and later in superficial stroma, with less density in the midstroma. The central extent may show crossing lines of darkness
Figure 60-4 Arcus senilis. A, Corneal arcus in an elderly man. B, Histologic section shows that the lipid is concentrated in the anterior and posterior stroma as two red triangles, apex to apex, with the bases being Bowman’s and Descemet’s membranes, both of which are infiltrated heavily by fat (red staining), as is the sclera. (From Yanoff M, Fine BS. Ocular pathology, ed 5. St. Louis: Mosby, 2002.)
or lessened deposition, similar to the patches seen in the central cornea in crocodile shagreen, discussed later. The roughly circular path of the arcus may deviate centrally in areas of corneal vascularization. The arcus is almost always bilateral. It may be asymmetric when carotid vascular disease on one side is associated with decreased arcus or when arcus is increased in eyes with chronic hypotony.
The frequent designation of corneal arcus as arcus senilis recognizes its association with aging. Arcus is the most common of the corneal degenerations. In men, it occurs with increasing frequency from the ages of 40–80 years, in 90% of normal men between 70 and 80 years of age, and in essentially all those older than 80 years. In women a similar pattern is seen, but with a delay of about 10 years.
The deposits of arcus are made up of extracellular steroid esters of lipoproteins, most of a low density. Lipid material leaks from limbal capillaries, but its central flow is limited by a functional barrier to the flow of large molecules in the cornea, which keeps the deposits in their peripheral location. 
The most important systemic association of corneal arcus is with aging. Also, good evidence exists for an association with increased plasma cholesterol and low-density lipoprotein cholesterol, particularly in men younger than 50 years (arcus juvenilis). Young patients who have arcus also have an increased risk for type IIa dyslipoproteinemia but a decreased risk for type IV. Men with arcus juvenilis have a fourfold increased relative risk of mortality from coronary heart disease and cardiovascular disease. Arcus in young men therefore is a useful clinical indication for the need for lipid and cardiovascular evaluation.  In older patients, including diabetics, arcus does not correlate with mortality. 
Figure 60-5 Dense lipid keratopathy. Note the central and peripheral lipid deposits that followed zoster keratitis with vascularization.
Lipid keratopathy may be peripheral, central, or diffuse but is discussed here because of its similarity to arcus. It occurs rarely in a primary form and more often in a secondary form; the latter appears as a white or yellow stromal deposit separated by a narrow, clear zone from corneal stromal neovascularization  ( Fig. 60-5 ). It is often denser than arcus and may appear rather suddenly as a circular deposit at the end of long-standing stromal vessels. Such lipid deposits have been known to follow corneal edema, as in hydrops. Histopathologically, the material consists of intra- and extracellular lipids, similar to those of arcus.
Primary lipid keratopathy has features of a corneal dystrophy. It is usually bilateral and occurs in a previously normal cornea. Central lipid, often with cholesterol crystals, may severely decrease vision and warrant penetrating keratoplasty.
Vogt’s White Limbal Girdle
Vogt described many of the corneal degenerations in his classic atlas of 1930. He was the first to describe two types of limbal girdle—white, arc-like opacities in the cornea central to the limbus in the 3 and 9 o’clock positions. What Vogt described as type I is probably a mild, early form of calcific band keratopathy with a peripheral clear zone and scattered clear holes. The much more common type II lacks a peripheral clear zone between the arc and the limbus and consists of fine, white radial lines, located nasally more often than temporally ( Fig. 60-6 ). As with most degenerations, this condition increases in prevalence with age. It is present in normal eyes in 50% of those who are 40–60 years of age and increases to essentially 100% in those older than 80 years. 
Histologically, Vogt’s limbal girdle type II is made up of hyperelastotic and hyaline deposits peripheral to Bowman’s membrane. These findings are similar to those seen in pinguecula and pterygium.
Senile Corneal Furrow Degeneration
A peripheral corneal furrow that occurs between corneal arcus and the limbus in the elderly is found, but rarely. The lucid interval peripheral to arcus may appear to be furrowed because of the clarity of the superficial cornea, but it was considered to be falsely thinned by Vogt. Rarely, true thinning with no inflammation, vascularization, or induced corneal astigmatism can occur in this region, usually in the very elderly. It requires no therapy, but it should be considered when cataract incisions are made in these patients.
Figure 60-6 Vogt’s limbal girdle. The fimbriated peripheral corneal opacity is visible in the 9 o’clock position (arrow).
Terrien’s Marginal Corneal Degeneration
Terrien’s degeneration is a condition with marginal corneal ectasia and was described originally as a dystrophy. It occurs at any age, from children to the elderly, although it is said to occur most frequently in middle-aged to elderly men. Most cases are bilateral, although the timing of development on each side may be different.
Terrien’s degeneration initially arises with peripheral corneal haze, usually superiorly. This gradually vascularizes superficially and is followed by corneal thinning, typically with a sloping central edge and a fairly steep peripheral edge to the resultant furrow. A lipid deposit is present along the central edge ( Fig. 60-7 ). Slowly, this progresses around the limbus and somewhat centrally—the progression may occur over many years or decades. Astigmatism develops from the associated corneal flattening, which may be irregular, and the resulting visual deterioration is more likely than other symptoms to lead to presentation. Usually no pain or inflammation occurs, although some patients have periodic episodes of redness and discomfort that respond to topical corticosteroid treatment. A pseudopterygium, often in an axis other than that of a typical pterygium, occurs in many patients. Corneal thinning may progress, despite intact epithelium, to the point at which a deep corneal break leads to hydrops or even to frank perforation.  In such cases, corneal inlay lamellar grafting or excision of the ectatic tissue with direct resuturing may be indicated. Fuchs’ superficial marginal keratitis has similar findings but more conjunctival involvement and is more localized (see Chapter 61 ).
Although the cause of Terrien’s disease is unknown, it is likely to be different from the causes of most degenerations that occur with age. Histopathologically, the chief findings are those of stromal thinning, fibrosis and vascularization. Phagocytosis of corneal stromal collagen may be seen.
Pellucid marginal corneal degeneration is another condition with peripheral corneal thinning. It is not a true degeneration but rather a variant of keratoconus (see Chapter 59 ).
Peripheral Corneal Guttae
The corneal endothelium undergoes degeneration with age, as manifested by a decreasing endothelial cell density and thickening of the posterior, nonbanded layer of Descemet’s membrane. Degenerating endothelial cells produce localized nodular thickenings of Descemet’s membrane, known as guttae. The incidence of central guttae increases with age. The relationship of central guttae to Fuchs’ corneal endothelial dystrophy is discussed elsewhere with the corneal dystrophies. Peripheral guttae, known as Hassall-Henle warts, are visible in normal adult
Figure 60-7 Terrien’s marginal corneal degeneration. A, Note the lipid deposit along the central edge. B, Histologic section shows limbus on the left (iris not present) and central cornea to the right. Note marked stromal thinning. (From Yanoff M, Fine BS. Ocular pathology, ed 5. St. Louis: Mosby, 2002.)
corneas and are thought to be truly degenerative and unrelated to Fuchs’ dystrophy (see Chapter 57 ). They are not associated with functional corneal changes.
Calcific Band Keratopathy
Band keratopathy is a common corneal degeneration that can occur at any age and can occur peripherally or centrally. Whereas primary idiopathic forms rarely occur, it most commonly occurs in eyes with chronic disease, particularly uveitis, glaucoma, keratitis, or trauma. It also occurs with elevated serum calcium or phosphate. A toxic form resulting from mercurial preservatives in pilocarpine has been described. Associated systemic diseases include sarcoidosis, hyperparathyroidism, vitamin D toxicity, and extensive metastatic neoplasm to bone, all of which are associated with elevated serum calcium. In children, band keratopathy may be the presenting sign of chronic uveitis as a result of juvenile rheumatoid arthritis. It may also occur in patients with chronic renal failure from secondary hyperparathyroidism. Local corneal damage has occurred as a result of intraocular silicone oil, viscoelastics manufactured in the past with high phosphate levels, and phosphate forms of corticosteroids.   
The mechanism of calcium deposition in the cornea is unknown, but it is associated with corneal exposure, as deposition occurs primarily in the exposed area. It may result from precipitation left as tears evaporate or because of a lower pH in this region.
As the name implies, calcium is deposited in the cornea as a horizontal band that begins near the corneal periphery and appears
Figure 60-8 Band keratopathy. A, Calcium deposits in the cornea of a 13-year-old with juvenile rheumatoid arthritis. B, A fibrous pannus (P) is present between the epithelium (E) and a calcified Bowman’s membrane (CB). Some deposit is also present in the anterior corneal stroma (S). (From Yanoff M, Fine BS. Ocular pathology, ed 5. St. Louis: Mosby, 2002.)
as a hazy deposit in the peripheral stroma separated from the limbus by a clear zone ( Fig. 60-8 ). The more central areas have clear circles where Bowman’s membrane is traversed by nerve endings. Gradually, the deposits move centrally, although the central areas may occasionally occur first. The most severely affected area is centered on the junction of the middle and inferior thirds of the cornea, the area of greatest exposure to the atmosphere. The deposits begin as a gray haze but can become densely white with a rough, pebbly surface that elevates the epithelium and results in pain, foreign body sensation, recurrent corneal erosions, and decreased vision. The rate of development is variable; it may take many years, although it may occur rapidly in very dry eyes.
Histopathologically, calcium is deposited as the hydroxyapatite salt in the epithelial basement membrane, basal epithelium, and Bowman’s membrane.  The deposits are usually extracellular, although hypercalcemia may cause intracellular epithelial accumulation.
Band keratopathy usually does not decrease vision and requires no treatment or only treatment of the underlying condition. If persistent discomfort or decreased vision occurs, the central deposits may be removed. Traditionally, this is done by removal of the epithelium over the deposits and the application of 0.05?mol/l disodium ethylenediaminetetraacetic acid as a chelator of calcium. After several minutes the surface is rubbed with a sponge or blade. This process is repeated until the central cornea becomes clear. Coverage of the resulting corneal defect by transplanted amniotic membrane may help to restore the surface. A diamond burr may be used to help remove dense deposits.
Figure 60-9 Spheroidal degeneration. Central spheroidal droplets in the cornea of an eye that is blind from glaucoma.
Excimer laser phototherapeutic keratectomy may also be used to remove band keratopathy, although visual improvement is often limited by the underlying disease.
Spheroidal degeneration may have a distribution in the cornea similar to that of band keratopathy, and it also occurs in the conjunctiva. It has been given a variety of names, of which the most commonly used are climatic droplet keratopathy, hyaline degeneration, and local designations such as Labrador keratopathy.  Spheroidal degeneration occurs as a primary corneal form, a secondary corneal form in eyes with prior keratitis or trauma, and a conjunctival form. Its frequency varies with geographic location and increases with age. It occurs most often in areas that have high sunlight exposure and sunlight reflection off snow or sand, in combination with wind-driven corneal damage by snow and sand. It is twice as prevalent in men as in women. Prevalence varies from 6% in England to over 60% in males in Labrador. It is thought to be a result of ultraviolet light exposure and may also be associated with blue-light exposure.  Drying of the cornea and repeated corneal trauma are thought to be risk factors. An association exists with conjunctival pinguecula, which is thought to have a similar cause. The secondary forms occur with corneal scars after keratitis or trauma, lattice corneal dystrophy, and glaucoma.
Typically, spheroidal degeneration is characterized by the presence of fine droplets, yellow or golden in color, beneath the conjunctival or corneal epithelium ( Fig. 60-9 ). The droplets appear oily, although they are not of lipid origin. They may be clear but often become cloudy or opaque over time. In the cornea they may occur along the edge of scars. In the primary form, they begin peripherally and advance toward the center in the palpebral fissure area. As the condition advances, the droplets become larger and more nodular and lift the central corneal epithelium. Three stages of the primary form have been described:
• Grade I—fine shiny droplets are present only peripherally without symptoms.
• Grade II—the central cornea is involved and vision may be as low as 20/100 (6/30).
• Grade III—there are large corneal nodules and vision is no better than 20/200 (6/60).
These forms are always bilateral. Stage III disease may be rapidly progressive followed by ulceration of involved areas of cornea, with secondary bacterial infection.
In histologic sections the deposits of spheroidal degeneration appear as extracellular amorphous globules, which may coalesce to form larger masses in Bowman’s membrane. These globules are made up of a protein material with elastotic features, as in pinguecula. The source of the protein is unknown, but it has
Figure 60-10 Hudson-Stähli line. Thin horizontal brown line in inferior cornea of a healthy 57-year-old male. (Courtesy of the photography department, WK Kellogg Eye Center, University of Michigan.)
been postulated to result from the action of ultraviolet light on proteins that diffuse into the stroma from limbal vessels. 
The majority of cases of spheroidal degeneration are asymptomatic. In those who have visual loss from central corneal lesions, as occurs frequently in the developing tropical areas, superficial keratectomy and lamellar or penetrating keratoplasty have been used. Reports of excimer laser phototherapeutic keratectomy in the climatic form have shown encouraging results.
Iron deposition occurs in the deep corneal epithelium in several clinical situations in which the smooth spreading of the tear film is disturbed. The prototype is the Hudson–Stähli line, which is located at the junction of the middle and lower thirds of the cornea ( Fig. 60-10 ). It is yellow-brown in color and curves downward at its center. It is usually about 0.5?mm wide and 1–2?mm long. It is seen most clearly in blue light as a black line. Hudson–Stähli lines occur in most patients over the age of 50 years and decrease in density and frequency after the age of 70 years. Similar iron deposition occurs at the base of the cone in keratoconus (Fleischer ring), around filtering blebs (Ferry line), central to pterygium (Stocker line), and around Salzmann’s nodules. Iron lines occur within the margin of corneal grafts, between radial keratotomy scars, and following laser in situ keratomileusis (LASIK). It is postulated that altered tear flow secondary to distorted corneal shape is a factor in the formation of these lines and that epithelial migration patterns affect the shape of the Hudson-Stähli line. The source of the iron is unknown, but it most likely comes from the tear film.
Histologically, the iron associated with these conditions is deposited intracellularly in the corneal epithelial cells as a ferritin-like material, possibly hemosiderin. The Hudson-Stähli lines do not affect vision or cause any symptoms and thus require no treatment.
Coats’ white ring is an iron deposition that occurs just deep to the corneal epithelium in the anterior portion of Bowman’s membrane. It appears as a tiny ring of white dots, most often inferiorly. It is thought to result from previous iron deposition by a corneal foreign body and occurs long after resolution of the corneal iron ring. It has no symptoms.
Anterior or posterior polygonal opacities in the corneal stroma occur as a consequence of aging. Crocodile shagreen was first described by Vogt in an elderly woman who had a gray opacity of the central cornea, with opacities separated by darker clear zones. The pattern resembles that of crocodile skin and is thought to be
Figure 60-11 Posterior crocodile shagreen. A mottled, gray pattern is visible in the central cornea.
related to the oblique insertion of the collagen lamellae that constitute the corneal stroma. The same pattern is transmitted to the normal corneal epithelium and may be seen after fluorescein is applied to the cornea and pressure applied through the closed lid, in hypotony of the globe, and in contact lens wearers with keratoconus. No information is available on the incidence of this degeneration, but it is a very common, although frequently subtle, finding in older patients. The anterior form is thought to be more common than the posterior, but posterior crocodile shagreen is similar, although it occurs in the deep central stroma ( Fig. 60-11 ). The opacities in posterior crocodile shagreen may occur peripherally, in which case they may be indistinguishable from the central extension of corneal arcus.
Histology is rarely available as surgical treatment is almost never indicated. Postmortem histology shows a serrated configuration of collagen lamellae in the stroma with widely spaced collagen fibers rather than any abnormal deposition of material.
Familial forms of posterior crocodile shagreen have been described in a dominant juvenile form and in a form associated with X-linked megalocornea. Central cloudy dystrophy of François appears to be similar, but it is a true dystrophy that is inherited dominantly. This dystrophic form rarely interferes with vision (see Chapter 59 ).
Like many of the other degenerations, this common but subtle finding was described by Vogt. It occurs in the corneas of older patients and is always an incidental finding as it causes no symptoms. The corneal opacities in this condition are very fine, dust-like dots of white or gray color in the deep central stroma, just anterior to Descemet’s membrane. The name farinata, meaning “like wheat flour,” refers to the appearance of the dots. The bilateral deposits are very difficult to visualize at the slit lamp, except by retroillumination. The cause of the condition is unknown. The histology of similar conditions suggests that the deposits may be composed of lipofuscin in stromal keratocytes. 
Salzmann’s Corneal Degeneration
This degenerative condition was described originally as a dystrophy. It may occur at any age but is primarily a condition of the elderly. It develops in corneas with previous keratitis but often several decades later. It has been associated particularly with past phlyctenular keratitis but may also follow interstitial keratitis, vernal keratitis, trachoma, or Thygeson’s superficial punctate
Figure 60-12 Salzmann’s nodular degeneration. Severe corneal involvement in an elderly woman.
keratitis, or it may occur with no history of prior corneal disease. It may be unilateral or bilateral and occurs more often in women than in men.
Salzmann’s degeneration is characterized by the presence of white to gray or light blue nodules that elevate the epithelium in the superficial corneal stroma ( Fig. 60-12 ). They may be single or occur as clusters in a circular array, often at the edge of old corneal scars. Each nodule is about 0.5–2?mm in diameter, not vascularized, and separated from other nodules by clear cornea. An epithelial iron line may outline the base of the lesion. The onset of the lesions is gradual, over many years, during which time they increase in both size and number. They may decrease vision as they encroach upon the central cornea or, more often, as they alter the corneal shape and may be associated with recurrent corneal erosions.
Histologic examination of excised nodules shows thinned epithelium that overlies hyalinized avascular collagen. Bowman’s membrane is damaged or focally absent and replaced by material that is similar to basement membrane. Usually, evidence is seen of old keratitis in the surrounding stroma.
Many elderly patients who have peripheral Salzmann’s nodules are asymptomatic and require no treatment. If vision is altered or if recurrent erosions are frequent, the nodules may be removed. Often, they may be peeled from the underlying stroma. Excimer laser phototherapeutic keratectomy has been used to remove these lesions, with success in improving vision. In the past, lamellar or penetrating keratoplasty has been used. Recurrences have been found after all forms of treatment.
Corneal Amyloid Degeneration
Amyloid is a group of hyaline proteins deposited in tissues in a variety of systemic and localized conditions. These conditions may be primary or secondary, localized or systemic, and familial or nonfamilial. The deposits of proteins may be derived from immunoglobulin light chains as in primary systemic amyloidosis, from amyloid A protein in secondary amyloid, from some forms of albumin in familial amyloidosis, and as a protein known as AP. Primary systemic amyloidosis causes heart failure, neuropathies, and other disorders. Secondary systemic amyloid follows long-standing inflammatory diseases such as tuberculosis or syphilis. Nonfamilial localized amyloidosis of a primary form can present with conjunctival or lid nodules. Familial localized amyloidosis is seen in the cornea as lattice, Avellino, and gelatinous drop-like corneal dystrophies discussed in Chapter 59 .
Figure 60-13 Polymorphic amyloid degeneration. Glassy, fine deep corneal deposits in the central cornea of an elderly woman.
The degenerative forms of amyloid seen in the cornea and conjunctiva are secondary, localized, and nonfamilial. These occur as nonspecific corneal deposits that follow corneal trauma or keratitis. They may also follow chronic intraocular inflammation. Usually, they are not diagnosed clinically as amyloid deposits but are seen histopathologically, often in nonspecific corneal opacities. Histologic diagnosis can be made with Congo red staining of extracellular hyaline deposits or with immunofluorescence staining for specific amyloid proteins.
A more specific form of corneal amyloid degeneration has been described as polymorphic amyloid degeneration. Usually, this condition is an incidental finding in the elderly. It is characterized by the presence of glass-like deposits in the deep central corneal stroma, which often indent Descemet’s membrane. The deposits are punctate or rod-like and may appear identical to the deposits of lattice dystrophy, although they are usually much less dense ( Fig. 60-13 ). They are bilateral, generally occur after the age of 50 years, and do not affect vision. Histologically, they appear similar to lattice dystrophy deposits and are composed of amyloid. The cause is unknown and the condition requires no treatment.
Another stromal deposition with features of both spheroidal degeneration and amyloid deposition has been called climatic proteoglycan stromal keratopathy.  This has been described in Saudi Arabian patients, and the risk factors are similar to those of spheroidal degeneration. The patients have bilateral, horizontal, oval, central anterior stromal, ground glass haze. Some have refractile stromal lines. Both proteoglycan and amyloid have been found histopathologically. This condition does not usually affect vision.
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