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.