The eyes are complex vision receptors situated in a pair of bony cavities in the skull—the orbits—which open anteriorly to the exterior and posteriorly for the entry and exit of nerves and blood vessels. The main nerve—the optic nerve—carries visual impulses from the retina to the brain.
The anterior covering of the eyeball is the transparent cornea, which permits entry of light into the eyeball through the lens, which is the focusing mechanism. The cornea is continuous at the limbus with the sclera. The conjunctiva lines the inner surface of the eyelids (palpebral conjunctiva) and is reflected onto the sclera (bulbar conjunctiva). When the eyelids are closed, the conjunctiva forms a sac that is lubricated by tears, the secretion of the lacrimal gland, situated in the lateral part of the orbit.
The eyeball is separated from orbital bone by connective tissue, muscles, nerves, and blood vessels. The eyelids, which protect the front of the eye, are covered with skin on the outside and conjunctiva on the inside.
Many different types of pain may occur in eye diseases. In conjunctival and corneal inflammation, burning or itching of the eye is commonly associated with increased sensitivity to light (photophobia). Deep aching pain occurs in angle-closure glaucoma and inflammation of the uveal tract. Pain in acute glaucoma may be so severe as to cause vomiting. Headache may accompany conditions of disturbed vision.
Decreased visual acuity (amblyopia) is a feature of many ocular diseases. Spots and halos before the eyes occur in early cataract. Halos may also occur in glaucoma. Diminution of the visual field may signify disease of the retina, the optic disk, or the visual neural pathways, which include the optic nerve, chiasm, radiation, and visual cortex. Night blindness may result from vitamin A deficiency and retinal degenerative diseases. Double vision (diplopia) is a feature of eye muscle dysfunction.
Eye discharge may represent increased tearing (eg, in allergy) or inflammation of the conjunctiva. Microscopic examination of the discharge shows the type of inflammatory cells present and the presence of viral and chlamydial inclusions when these agents are involved. The presence of numerous eosinophils is typical of allergic conjunctivitis, while neutrophils dominate in acute infectious conjunctivitis. Gram stain for bacteria and potassium hydroxide preparations for fungi are of value in some cases.
Inspection of the eyes may disclose evidence of strabismus (muscle imbalance), hemorrhage, congestion, jaundice, swelling, displacements of the eye such as proptosis (forward displacement), and the presence of tumors. Ophthalmoscopic examination may reveal abnormalities of the anterior chamber (eg, hypopyon and hyphema—pus and blood, respectively, in the anterior chamber), lens (eg, early cataract, dislocation), vitreous (eg, hemorrhage), retina (eg, diabetic and hypertensive retinopathy, retinal degenerative diseases, detachment, hemorrhages, exudates, changes in retinal vessels), and optic disk (eg, optic atrophy, papilledema).
The skin covering of the eyelids is subject to a wide variety of diseases, the most important of which is basal cell carcinoma. Low-grade inflammation of the lid margins is termed blepharitis. More specific diseases of the eyelids are discussed below.
A sty is an acute suppurative inflammation of the hair follicle or associated glandular structures—the sebaceous glands of Zeis and the apocrine glands of Moll. It is usually caused by Staphylococcus aureus and produces a painful localized abscess (Figure 33-1), which is cured by rupture or extraction of the involved eyelash to effect drainage.
Internal hordeolum of the upper eyelid.
A chalazion is a common chronic inflammatory process involving the meibomian glands. It is believed to be caused by duct obstruction, leading to retention of secretions, infection, and chronic inflammation with macrophages, lymphocytes, and plasma cells. Clinically, it produces an indurated mass that may be mistaken for a neoplasm.
Xanthelasma, a small yellow plaque composed of collections of lipid-laden foamy macrophages in the subepithelial zone, occurs in some hyperlipidemic conditions. There are usually multiple lesions.
Several types of cyst occur in the eyelid. Congenital dermoid cysts occur along the lines of fusion of the facial skin folds, most often at the external angle of the upper eyelid. Microscopically, the cysts are lined by skin containing dermal glands. Acquired cysts arising in ducts of glands (eg, eccrine and apocrine hydrocystomas) and epidermal inclusions (epidermal cysts) are common.
Basal cell carcinoma is the most common malignant neoplasm of the eyelid. It occurs much more commonly in the lower than in the upper lid. The skin about the eye is the most common location for basal cell carcinoma. These tumors begin as small nodules that grow and ulcerate, forming an enlarging ulcer with an elevated pearly margin (Figure 33-2). Microscopically, they are composed of nests of small hyperchromatic cells resembling basal cells. They invade locally and may extend deeply into the orbit, but they do not metastasize. Squamous carcinoma is uncommon in the eyelids.
Basal cell carcinoma of the lower eyelid, showing an ulcer with raised edges. This is the most common neoplasm of the eyelids and the most common location for basal cell carcinoma.
Meibomian gland carcinoma (sebaceous carcinoma) occurs chiefly in the upper eyelid, which is the predominant location of meibomian glands. These tumors appear as slowly growing yellowish masses that may resemble a chalazion. Progression causes erosion of the lid margin or conjunctiva and the appearance of a large lobulated mass. Microscopically, the tumor forms large invasive nests and sheets of cells with abundant cytoplasm. The diagnostic feature is the presence of large cells with vacuolated cytoplasm that contain lipid (demonstrable with lipid stains on frozen sections). Like other adenocarcinomas, meibomian gland carcinoma may spread laterally in pagetoid fashion into the epidermis of the eyelid. Meibomian gland carcinoma is important to distinguish from squamous and basal cell carcinoma because it has a more aggressive biologic behavior. Lymph node metastasis is common.
The conjunctiva is lined by a thin, transparent, nonkeratinizing stratified squamous epithelium in which are found scattered mucous cells. The cornea is composed of nonkeratinizing stratified squamous epithelium, Bowman's layer, an avascular stroma, Descemet's membrane, and an underlying endothelium lining the anterior chamber.
Inflammation of the conjunctiva is called conjunctivitis and inflammation of the cornea is called keratitis; when both are involved, as is frequently the case, the term keratoconjunctivitis is used.
Conjunctivitis is common and has many causes (Table 33-1).
Table 33–1. Causes of Conjunctivitis and Keratitis. ||Download (.pdf)
Table 33–1. Causes of Conjunctivitis and Keratitis.
Trauma, foreign bodies
Pathology & Clinical Features
Acute bacterial conjunctivitis is characterized by pain, hyperemia appearing as vascular injection (red eye), and a purulent discharge in which numerous neutrophils are present. Neisseria species, pneumococcus, and Haemophilus aegyptius infections are common. Ophthalmia neonatorum results from infection of the fetus with Neisseria gonorrhoeae during delivery through the birth canal. Ulceration occurs in severe cases, and when this involves the cornea visual impairment may occur.
Viral keratoconjunctivitis is most frequently caused by adenoviruses and herpes simplex virus (Figure 33-3).
Corneal scar caused by recurrent herpes simplex keratitis.
Inclusion conjunctivitis (“swimming pool conjunctivitis”) is common worldwide. It is characterized clinically by acute inflammation with pain, red eye, and discharge and histologically by accumulation of lymphocytes in the conjunctiva. It is caused by chlamydiae, which may be demonstrated as cytoplasmic inclusions in infected cells in the exudate. The disease is transmitted via contaminated hands, shared towels, and infection of the fetus during delivery through an infected birth canal. It is self-limited, with recovery occurring in all cases after a few days of discomfort.
Trachoma is a much more serious chlamydial infection in which there is long-term destruction of the cornea, leading to blindness in cases that are not treated early. The acute conjunctival inflammation progresses to a chronic phase in which there may be epithelial hyperplasia, lymphocytic infiltration, and pannus formation—the last an inflamed mass of granulation tissue that replaces the superficial layers of the cornea and results in blindness. Trachoma is the most common cause of blindness in underdeveloped tropical countries.
Acanthamoeba keratoconjunctivitis. Epidemics of keratoconjunctivitis caused by amebae of the species Acanthamoeba have been traced to the use of contaminated contact lens cleaning fluids.
Allergic conjunctivitis. Allergic conjunctivitis—also called vernal (“spring”) conjunctivitis—is typically seasonal in occurrence due to pollens in the environment and is associated with hay fever. Histologically, it shows goblet cell hyperplasia and infiltration by lymphocytes and eosinophils.
Phlyctenular conjunctivitis is a delayed hypersensitivity response to antigens of bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus. It is characterized by an elevated, hard, red triangular plaque at the limbus, which ulcerates and then heals in about 2 weeks. Corneal involvement may cause scarring and visual disturbances.
The diagnosis of conjunctivitis can be made clinically based on the presence of conjunctival injection and discharge. Keratitis is diagnosed by examination; invisible epithelial lesions may be outlined by fluorescein staining. The etiologic agent is identified by culture and microscopic examination of conjunctival discharge and scrapings from corneal lesions. A finding of chlamydial or viral inclusions is diagnostic. Amebic trophozoites are present, often in large numbers, in Acanthamoeba keratoconjunctivitis.
Degenerative Conjunctival & Corneal Conditions
Pinguecula is a common degenerative disease caused by ultraviolet solar radiation and is similar to solar-induced changes in the skin, with epithelial atrophy, degeneration of collagen, and hyalinization of elastic tissue (see Chapter 61: Diseases of the Skin). The exposed interpalpebral part of the conjunctiva is chiefly affected. The atrophic epithelium may show precancerous dysplastic changes.
Pinguecula appears clinically as a thickened, yellowish area in the conjunctiva. It may become secondarily infected and ulcerate. The risk of squamous carcinoma is small.
Pterygium is pathologically similar to pinguecula but differs in that it affects the sclerocorneal junction (limbus) and may extend into the cornea as a layer of vascularized connective tissue, producing corneal opacification and visual impairment. In the cornea, there is replacement of Bowman's layer by collagen and elastic tissue. Pterygia also have a greater tendency to recur after excision. The incidence of secondary infection, ulceration, and epithelial dysplasia is low.
In squamous metaplasia, the normally thin, transparent nonkeratinized squamous epithelium is replaced by a thick, opaque, keratinized squamous type. This appears as a pearly white plaque on the conjunctiva, sometimes called leukoplakia. Areas of squamous metaplasia are more often subject to infection and ulceration but are not precancerous.
Squamous metaplasia may be caused by (1) insufficiency of tears, as occurs in Sjögren's syndrome, which causes frictional damage of the conjunctiva; (2) protrusion of the eyeball (exophthalmos), which prevents eyelid closure and results in excessive irritation; (3) neuromuscular disorders in which paralysis of the eyelid muscles is a feature (facial nerve paralysis), leading to inability to close the eyes, again increasing irritation; and (4) vitamin A deficiency, which causes a basic abnormality of squamous epithelium, leading to thickening. The areas of squamous metaplasia in vitamin A deficiency are called Bitot's spots and commonly extend to involve the cornea; they may become infected, causing softening of the cornea (keratomalacia) and visual impairment.
Arcus senilis is a ring of fatty infiltration at the outer margin of the cornea, common in elderly individuals. A similar lesion occurs in younger patients with hyperlipidemia.
Neoplasms of the Conjunctiva
Benign neoplasms such as squamous papilloma, melanocytic nevus, hemangioma, and neurofibroma occur rarely on the conjunctiva as small masses of various colors. Benign lymphoid hyperplasia may also occur, leading to a conjunctival mass.
Squamous carcinoma of the conjunctiva is also rare. Most cases are believed to be the result of exposure to ultraviolet radiation, complicating the actinic lesions pinguecula and pterygium. The neoplastic process progresses through increasing grades of dysplasia to carcinoma in situ and then invasive squamous carcinoma.
Conjunctival squamous carcinoma usually invades superficially and almost never metastasizes. It has an excellent prognosis and is treated by limited local excision.
Conjunctival malignant melanoma is rare. It may occur (1) de novo, (2) in relation to a preexistent melanocytic nevus, or (3) in relation to an acquired melanocytic hyperplasia (lentigo). It presents clinically as a nodule that may or may not be pigmented. The more superficial lesions can be treated by local excision and have a good prognosis. With deeper invasion, lymphatic and vascular involvement commonly occurs, and the prognosis is guarded even following radical exenteration of orbital contents.
Mass lesions of the orbit cause forward displacement of the eyeball (proptosis). Because the lesion is behind the conjunctival sac, special techniques are required to obtain tissue for diagnosis.
Inflammatory pseudotumor is characterized by forward protrusion of the eyeball (proptosis), pain, swelling, and restriction of ocular movement. Histologically, there is edema, hyperemia, and infiltration of the orbital soft tissue with neutrophils, eosinophils, lymphocytes, and plasmacytes. The diagnosis is usually made when orbital exploration in a patient suspected clinically of having a neoplasm shows only nonspecific chronic inflammation and fibrosis. The cause is unknown.
Graves' disease (primary autoimmune hyperthyroidism) is commonly associated with exophthalmos as a result of edema and increased accumulation of mucopolysaccharides in the orbital soft tissues. The orbital muscles show marked myxoid change and weakness. The condition is usually bilateral and is believed to be caused by an autoantibody (exophthalmos-producing factor) that may persist even after the hyperthyroidism is treated (Chapter 58: The Thyroid Gland).
The lacrimal gland is situated in the lateral wall of the orbit and is rarely the site of pathologic processes. Sjögren's syndrome (see Chapter 31: The Oral Cavity & Salivary Glands) is characterized by autoimmune destruction of the gland associated with dry eyes due to failure of tear production. The autoimmune process usually causes atrophy of the gland; more rarely, the lymphocytic infiltration may produce a mass lesion (benign lymphoepithelial lesion). Primary neoplasms of the lacrimal glands are very rare and are similar to salivary gland neoplasms.
Primary Neoplasms of the Orbit
Malignant lymphoma is the most common malignant neoplasm of the orbit in adults. Most orbital lymphomas are low-grade B cell lymphomas (Chapter 29: The Lymphoid System: II. Malignant Lymphomas). An exception is Burkitt's lymphoma, an aggressive B cell lymphoma that occurs in children in Africa and often involves the orbit.
The diagnosis is established by histologic examination. Inflammatory lymphoid proliferations (pseu-dotumors) may be distinguished from lymphomas by immunologic methods (polyclonal versus monoclonal; Chapter 29: The Lymphoid System: II. Malignant Lymphomas).
Embryonal rhabdomyosarcoma is a rare orbital primary tumor, occurring mainly in children. It is highly malignant, with a rapid growth rate. The diagnosis is made by demonstrating an undifferentiated neoplasm in which primitive rhabdomyoblasts may be identified. Untreated, it is rapidly fatal. With chemotherapy and radiation, orbital embryonal rhabdomyosarcomas can be controlled and sometimes cured.
Optic nerve glioma is a rare neoplasm of the optic nerve, usually affecting the intraorbital part of the nerve. It is commonly a well-differentiated, very low grade, fibrillary astrocytoma that grows slowly over several years. Most cases occur in children, often in association with generalized neurofibromatosis (von Recklinghausen's disease).
Primary neoplasms of bone such as osteoma and histiocytosis X (Hand-Schüller-Christian disease and eosinophilic granuloma) and metastatic neoplasms such as neuroblastoma in children and metastatic carcinoma in adults may present as orbital masses.
The eyeball itself is composed of several layers and compartments. The retina is the inner light-sensitive layer and is composed of modified neurons, the axons of which form the optic nerve. The choroid, which is pigmented, and the fibrous sclera are the outer layers of the eyeball.
The lens is attached to the sclera by the ciliary muscle, contraction of which controls the focal length of the lens. The lens and ciliary muscle separate the anterior part of the eyeball, filled with aqueous humor, from the posterior part, which is filled with vitreous. The iris projects into the aqueous humor in front of the lens, partially separating the aqueous humor into anterior and posterior chambers. The iris, by its contraction, controls the amount of light entering the eye and also gives the eyes their color. The circular black opening in the center of the iris through which light passes into the eye is the pupil. The choroid, iris, and ciliary body comprise the uveal tract.
Inflammatory Conditions of the Eyeball
Inflammations of the eye may involve one or more—or all—components of the eyeball.
Pyogenic bacteria such as staphylococci gain entry into the eyeball following penetrating injuries to the eye or, less often, from orbital cellulitis or via the bloodstream from an infective focus elsewhere in the body. Acute endophthalmitis or panophthalmitis results, with swelling and a severe neutrophil infiltration. Untreated, there may be severe destruction with softening and collapse of the eyeball (phthisis bulbi).
Toxoplasma gondii infection involves the choroid and retina and occurs either as a congenital transplacental infection or as an acquired infection.
Congenital toxoplasmosis may cause neonatal or intrauterine death from encephalitis; survivors frequently show chorioretinitis, sometimes as the only manifestation of congenital toxoplasmosis. The organism persists in the choroid as pseudocysts, causing symptoms in childhood and early adult life.
Acquired toxoplasmosis occurs in adults. Ocular involvement is common, and the eye may be the only clinical site of involvement.
Pathologically, there is focal coagulative necrosis of the retina and choroid, with granulomatous inflammation and fibrosis. Toxoplasma can be identified as small crescent-shaped trophozoites and as larger pseudocysts.
Ocular larva migrans is usually caused by larvae of Toxocara canis (a dog nematode) that reach the interior of the eye through the uveal or retinal blood vessels. Children exposed to dog feces are chiefly affected. It causes a granulomatous endophthalmitis with large numbers of eosinophils around the larvae. Marked fibrosis frequently causes retinal detachment and visual loss.
Noninfectious Inflammatory Conditions
Sarcoidosis produces both an acute iridocyclitis, with fever and pain, and a chronic granulomatous disease, with corneal opacification and visual impairment.
Rheumatoid arthritis typically produces scleritis and uveitis, in which foci of necrotic collagen surrounded by palisading histiocytes resemble ill-defined rheumatoid nodules.
Both ulcerative colitis and Crohn's disease are associated with nonspecific chronic iritis.
Ankylosing spondylitis is associated with anterior uveitis in 20–50% of cases.
Sympathetic ophthalmia is an uncommon diffuse granulomatous uveitis that affects both eyes after a penetrating injury (or surgery) to one eye. It is believed to be the result of an immunologic reaction against antigens released or altered in some unknown way by the injury. The entire uveal tract is infiltrated by lymphocytes and plasma cells and may show ill-defined epithelioid cell granulomas. Severe visual loss commonly occurs.
Behet's syndrome (uveitis plus oral and genital lesions) and Reiter's syndrome (conjunctivitis, uveitis, arthritis, and urethritis) probably represent postinfectious autohypersensitivity responses.
Miscellaneous Diseases of the Eyeball
Opacification of the lens, irrespective of cause (Table 33-2), is called a cataract (Figure 33-4). The lens is derived from surface ectoderm and consists of a mass of modified epithelial cells. It has no blood supply and derives its nutrition from the aqueous humor of the anterior chamber. Despite the fact that the oldest epithelial cells become compressed centrally throughout life, the lens normally remains transparent. Most individuals develop some lens opacification in later life (senile cataract). Whether this is an aging phenomenon or disease has not been elucidated.
Mature senile cataract seen through a dilated pupil.
Table 33–2. Principal Types and Causes of Cataract. ||Download (.pdf)
Table 33–2. Principal Types and Causes of Cataract.
Congenital, inherited (autosomal dominant), unilateral or bilateral.
Congenital, due to fetal infection, especially rubella.
Congenital, associated with chromosomal abnormalities: trisomy 13.
Radiation to the eye.
Trauma, including penetration and contusion.
Toxic, drug-induced: dinitrophenol, long-term steroids.
Senile (aggravated by solar radiation).
Diabetic (resembles accelerated senile cataract).
Pathologically, visible cataracts may occur with minimal changes in water content of cortical cells. With advanced or mature cataracts, the epithelial cells break down, fragment, and undergo dissolution. In diabetes, high glucose levels cause excess production of sorbitol within the lens. Sorbitol is not diffusible and exerts a strong osmotic effect, leading to water imbibition and ultimately to cell degeneration. In galactosemia, galactose is metabolized in the lens to dulcitol with similar results.
Clinically, cataracts cause progressive loss of visual acuity. Halos or spots in the visual field are early symptoms. Current treatment methods, which include extraction of the cataract and implantation of a prosthetic lens, are very successful.
Glaucoma is defined as an increase in intraocular pressure sufficient to cause degeneration of the optic disk and optic nerve fibers. Normal intraocular pressure as measured by tonometry (which measures the pressure required to cause flattening of the cornea to a specified amount) is 10–20 mm Hg; elevations in pressure are thought to have a dual effect, inducing deformational changes in the optic disk plus decreased retinal blood flow. However, the correlation between intraocular pressure and optic nerve damage is not exact.
Glaucoma is the result of an abnormality in the dynamics of aqueous humor circulation. Aqueous humor production occurs at the ciliary body, partly by diffusion from plasma and partly by active secretion by the epithelium of the ciliary processes. The fluid passes from the posterior chamber through the pupil to the anterior chamber and then peripherally to the angle between the iris and cornea. Absorption of aqueous humor occurs at the iridocorneal angle by the trabecular meshwork and canal of Schlemm.
Glaucoma is a common disorder, with about 2% of all people over 40 years of age affected. Visual loss is the most common effect. Of the many causes (Table 33-3), obstruction to the outflow of aqueous humor from the anterior chamber is most common (Figure 33-5). Glaucoma may occur as a complication of other diseases affecting the eye (secondary glaucoma) or as a primary disease.
Circulation of aqueous humor, showing pathogenesis of glaucoma. Arrows indicate the direction of flow of aqueous humor.
Table 33–3. Glaucoma: Classification and Causes.1 ||Download (.pdf)
Table 33–3. Glaucoma: Classification and Causes.1
Primary (most common)
Primary: Defects in canal of Schlemm, congenital and infantile
Secondary: In association with other congenital anomalies: aniridia, Marfan's syndrome, neurofibromatosis, pigmentary glaucoma (degeneration of iris releases pigment that blocks outflow)
Open (wide) angle glaucoma: Most common form, often familial; due to degeneration of canal of Schlemm, age > 40 years
Closed (narrow) angle or angle closure glaucoma: Blockage of the narrow anterior chamber by iris, especially when dilated at night; increase in lens size, causing further narrowing of anterior chamber
Several mechanisms; usually act through obstruction out-flow from anterior chamber
Adhesions from uveitis (anterior synechiae)
Adhesions from intraocular hemorrhage or trauma
Dislocation of lens
Retinal artery narrowing (or occlusion), especially in diabetes mellitus
Arteriovenous fistulas (producing a direct increase in pressure)
Primary Open-Angle Glaucoma
Primary open-angle glaucoma, also called simple or chronic glaucoma, is a slowly progressive bilateral disease of insidious onset. It occurs in individuals over 40 years of age and is responsible for over 90% of cases of primary glaucoma. It is characterized by a slow rise in intraocular pressure with subtle microscopic abnormalities in the canal of Schlemm. There is progressive degeneration of the optic disk, an increase in size of the blind spot (scotoma), and peripheral visual field loss, ultimately causing blindness. Examination of the optic fundus shows deepening and enlargement of the optic cup. Patients usually present at a late stage with severe loss of vision.
Treatment with pupillary constrictors such as pilocarpine and laser trabeculoplasty produce temporary improvement. Surgical treatment, which is indicated in severe cases, is successful in about 75% of cases in arresting visual loss.
Primary Angle-Closure Glaucoma
Angle-closure (closed-angle) glaucoma usually presents acutely. Many patients have a genetically determined anatomic variation that results in a shallow anterior chamber and a narrow anterior chamber angle (Figure 33-5). Increasing lens size, a normal occurrence with increasing age, causes forward displacement of the lens, further narrowing the angle. Acute attacks may be precipitated by dilation of the pupil (as in preparation for funduscopy), which further narrows the angle by thickening the periphery of the iris during pupillary dilation. Rapid increase of intraocular pressure causes severe pain, often accompanied by vomiting and rapid visual impairment. The optic disk is swollen, and complete blindness can occur within days.
Acute angle-closure glaucoma is an ophthalmologic emergency. Treatment with osmotic agents and pupillary constrictors such as pilocarpine is effective in interrupting the acute attack. Peripheral iridectomy by laser is effective both in the acute relief of symptoms and in preventing further episodes.
The lens is connected to the ciliary body by a bundle of collagen fibers called the zonular ligament and may be dislocated by trauma. Patients with abnormal collagen, as in Marfan's syndrome and homocystinuria, have weak zonular fibers that predispose to dislocation.
Anterior lens dislocation often causes obstruction to aqueous flow, leading to acute secondary glaucoma. Posterior dislocation of an intact lens does not cause severe symptoms except visual impairment. If the lens capsule is ruptured, lens protein may enter the bloodstream and stimulate antibody formation (lens protein contains antigens sequestered from the immune system during fetal life and is therefore regarded as foreign). This may result in immunologic endophthalmitis, with lymphocytic infiltration around the ruptured lens.
Retinitis pigmentosa is a group of degenerative disorders with variable inheritance, most often recessive. Expression is variable, but retinal degeneration usually begins in early life and progresses slowly to blindness at age 50–60 years. The degeneration begins in the peripheral part of the retina, causing progressive loss of the peripheral visual field. Central vision, including macular vision, is spared until the very late stage.
Pathologically, there is disappearance of the rod and cone layer and loss of ganglion cells. Loss of night vision is an early symptom. The fundus becomes slate-gray in color (Figure 33-6). There is no treatment at present.
Retinitis pigmentosa, showing clumped, scattered pigmentation of retina.
Retrolental Fibroplasia of Prematurity
Retrolental fibroplasia is caused by excessive oxygen, usually given for therapy of respiratory distress syndrome in premature infants. The immature retina is exquisitely sensitive to increased partial pressure of oxygen, responding with vasospasm and proliferation of small retinal vessels into the vitreous. Edema and leakage of blood leads to organization, fibrous traction on the retina, retinal detachment, and blindness. Careful control of oxygen therapy in the premature newborn has reduced the incidence of retrolental fibroplasia.
Vascular Diseases of the Retina
The retina is commonly affected in diseases of small vessels such as the microangiopathy of diabetes mellitus (Chapter 46: The Endocrine Pancreas (Islets of Langerhans)) and hypertension (Chapter 20: The Blood Vessels).
Vascular lesions causing occlusion of the central artery of the retina result in pale retinal infarction. Hemorrhagic infarction occurs when the central vein of the retina is occluded. Arterial emboli—either cholesterol emboli, derived from atheromatous plaques in the carotid circulation, or septic emboli in septicemic states such as infective endocarditis—may produce microinfarcts in the retina.
Detachment of the retina is separation of the neuroepithelial layer of the retina from the pigment layer, due either to fibrous contraction or to fluid collection between the two layers. Detachment deprives the neuroepithelial layer of its choroidal blood supply and causes degeneration within 4–6 weeks.
Retinal detachment may result from (1) extravasation of fluid from the choroid or retina in inflammations, neoplasms, and venous obstruction; (2) contraction of vitreous fibrous bands that have been formed by organization of vitreous hemorrhage, inflammation, or neovascularization (as occurs in retrolental fibroplasia and diabetic retinopathy); or (3) a hole in the retina, permitting passage of liquefied vitreous. Such holes are present in about 7% of individuals over 40 years. Trauma and severe myopia contribute to the occurrence of retinal detachment. Approximately 1% of myopic patients develop retinal detachment.
Clinically, retinal detachment causes sudden loss of part of the field of vision. The field defect depends on the site of detachment. Untreated, the detachment progresses, ultimately involving the entire retina and causing blindness. Laser treatment is effective in stopping the progression of retinal detachment and reversing the visual loss.
The term optic atrophy is applied to extreme pallor of the optic disk (optic nerve head). It usually reflects degeneration of optic nerve fibers and has many causes (Table 33-4). Primary optic atrophy—resulting from diseases of the optic disk—is distinguished from secondary optic atrophy, which is due to long-standing edema of the disk caused by increased intracranial pressure. Loss of vision follows unless the cause is treatable.
Table 33–4. Causes of Optic Atrophy. ||Download (.pdf)
Table 33–4. Causes of Optic Atrophy.
Ischemia: arteriosclerosis, giant cell arteritis
Increased intracranial pressure: chronic low-grade
Metabolic disorders: nutritional (vitamin B1, B6, B12 deficiencies); tobacco-alcohol amblyopia; chemicals (eg, methyl alcohol)
Trauma to optic nerve
Familial and congenital forms
Malignant melanoma occurs almost exclusively in white adults. In the United States and Europe, it is the most common intraocular malignant neoplasm. It is uncommon in Asia, Africa, and South America.
Intraocular malignant melanomas arise in the uveal tract (85% in the choroid, 10% in the ciliary body, 5% in the iris). They are composed of proliferating, invasive melanocytes, with several morphologic subtypes. Spindle cell type A tumor, composed of slender cells with elongated nuclei and no nucleoli, has the best prognosis (85% 10-year survival). Spindle cell type B tumors, composed of more ovoid spindle cells with nucleoli, have a slightly worse prognosis (80% 10-year survival). Epithelioid cell tumors, composed of large pleomorphic round cells with hyperchromatic nuclei, nucleoli, and a high mitotic rate, have a bad prognosis (35% 10-year survival). Over 50% of melanomas of the uveal tract contain mixtures of the above cell types.
Melanomas arising in the iris become visible as a black mass in the front of the eye and usually present at an early stage. Most melanomas of the iris are spindle cell type A tumors. The combination of early presentation and favorable histologic type gives iris melanomas a high survival rate (nearly 100%) after local surgical removal. Note that benign pigmented nevi also occur in the iris and are difficult to distinguish from melanoma clinically (Figure 33-7).
Pigmented lesion of the iris. Biopsy was necessary to determine whether this was a benign nevus (which it proved to be) or a malignant melanoma.
Melanomas arising in the ciliary body and choroid generally attain a large size before they are detected. They grow inward into the vitreous, producing detachment of the retina and visual impairment, which is the usual presenting feature. Such melanomas are usually treated by enucleation of the eye. Their prognosis depends mainly on the histologic type. In epithelioid melanomas, death is commonly due to distant metastases.
Retinoblastoma has a worldwide distribution and occurs in two forms: an inherited form (30%) and a sporadic form (70%). It occurs almost exclusively in children under 5 years of age, with a frequency of about 1:20,000.
Inherited cases commonly have bilateral retinoblastoma. More than 90% of sporadic cases have unilateral disease. Retinoblastoma is associated with a constant karyotypic abnormality (deletion of 13q−). Molecular studies show that a pair of recessive genes is involved, both of which must have undergone mutation to produce the disease. In the sporadic form of the disease, both mutations are acquired. In the hereditary form, one recessive gene is inherited in mutant form; the other suffers an acquired mutation, after which the tumor develops.
Retinoblastoma arises in the retina from primitive neural cells. It is an aggressive neoplasm, infiltrating the retina, extending into the vitreous (Figure 33-8) and along the optic nerve into the cranial cavity. Seeding of the cerebrospinal fluid may result in widespread dissemination in the subarachnoid space. Hematogenous spread also occurs. Microscopically, retinoblastoma is composed of undifferentiated small cells with a high nuclear to cytoplasmic ratio and hyperchromatic nuclei. Mitotic figures are frequent. The presence of Flexner-Winter-steiner rosettes composed of the neoplastic cells arranged in an orderly fashion around a central lumen is a diagnostic feature.
Retinoblastoma, showing a large retinal mass extending into the vitreous with multiple satellite nodules and invasion of the optic nerve.
The parent usually notices some peculiarity in the child's eye, commonly a white spot in the pupil (Figure 33-9; leukocoria—caused by the reflection of light entering the pupil by the retinal tumor). Increased size of the orbit due to the mass effect is a late sign. Fundal examination shows the presence of the neoplasm.
Retinoblastoma. Note the white spot in the right pupil resulting from reflection of light from the retinal tumor.
Without treatment, retinoblastoma causes rapid death in most cases. Patients with tumors restricted to the eyeball are treated by removal of the eye; if there is no scleral or optic nerve involvement, these patients have a good prognosis. Treatment with radiation and chemotherapy has improved the prognosis somewhat in more advanced cases. A significant number (1–2%) of retinoblastomas undergo spontaneous regression—the most frequent human neoplasm to demonstrate this phenomenon. Regression is associated with cessation of proliferation of the neoplasm followed by fibrosis. Patients with inherited retinoblastomas that have regressed represent a source of transmission of the abnormal gene to the next generation. Examination of the parents of a child with the inherited form of retinoblastoma commonly shows the presence of regressed tumor in one parent's retina.