Retinal and Choroidal Diseases

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[edit] Retinal and Choroidal Diseases

Uday R. Desai

Julian J. Nussbaum

Referrals to the ophthalmologist are often necessary because of the need for specialized examination modalities, including slit-lamp biomicroscopy, tonometry, and ophthalmoscopic examinations. In patients with vitreoretinal or choroidal disease, adequate examination requires the indirect ophthalmoscope and perhaps ophthalmic ultrasonography. Therefore suspected vitreoretinal or choroidal disease always mandates a referral to a vitreoretinal specialist. Awareness of the more common vitreoretinal abnormalities helps the primary care physician judge the urgency of different referrals. By identifying the patient's condition as vitreoretinal, the physician also may be able to refer the patient directly to the retinal specialist.

[edit] ANATOMY

The adult human eye averages 24 mm in diameter and consists of the anterior segment and posterior segment (Fig. 176-1). The posterior segment contains the retina, choroid, sclera, and vitreous body. The three layers of the posterior segment are the retina, choroid, and sclera (Fig. 176-2). The retina consists of the neurosensory retina, which is the sensory component of the ocular system, and the retinal pigment epithelium (RPE), which provides metabolic support. The retina has a vascular network that supplies the inner three fourths of the neurosensory retina. The choroid is composed of Bruch's membrane, choriocapillaris, middle and outer choroidal vascular layers, and the suprachoroidal space. Bruch's membrane is located adjacent to the RPE and is composed of basement membrane, collagen, and elastic layers. The vascular layers proceed outward from the choriocapillaris to the outer choroidal layer. This vascular network supplies the outer one fourth of the neurosensory retina and the RPE. The choroid contains connective tissue, melanocytes, and the short posterior ciliary nerves, which are responsible for pain sensation in this portion of the globe. Outside the choroid lies the sclera.

Figure 176-1 Sagittal section showing major structures of the eye.

Figure 176-2 Posterior segment layers of the eye. (From Johnson RN, et al: Fluorescein angiography: basic principles and interpretation. In Ryan SJ et al: Retina, ed 3, St Louis, 2001, Mosby.)

The three layers of the posterior segment surround the vitreous body, which has an average volume of 4 ml. The vitreous is a gel-like substance, the composition of which is 99% water. Other components include hyaluronic acid, which provides elasticity, and collagen, which provides strength. The vitreous is attached to the overlying retina early in life. The strongest attachments are at the vitreous base, which attaches to the peripheral retina, optic nerve, macula, and retinal vessels.

The vitreous can be visualized with slit-lamp biomicroscopy. The retina and choroid are seen with direct and indirect ophthalmoscopy (Fig. 176-3). The most prominent structure is the optic nerve, which is 1.5 mm wide and 1.75 mm high. It is seen as the yellow-red oval structure located nasal to the visual axis. From this nerve emerge the retinal arterioles and venules. Four pairs of vessels extend to each one of the following quadrants: superonasal, inferonasal, inferotemporal, and superotemporal. The superotemporal and inferotemporal arcades outline the retinal structure known as the macula. Within the macula is a 1500-μm-wide depression called the fovea centralis. Within the fovea is a 350-μm-wide area called the foveola, which contains only cone photoreceptors. Because cone photoreceptors have potential for good vision, the foveola is the only area of the retina with 20/20 visual potential.

Figure 176-3 Macular region of retina. Pointer identifies fovea.

The choroid lies deep to the retinal structures. The most visible of the choroidal structures are the four to seven vortex veins, which are the efferent arm of the choroidal circulation (Fig. 176-4). These orange vessels are located 2 to 3 disc diameters (1 DD about 1.5 mm) posterior to the equator of the eye. The other vascular structures of the choroid can be seen in lightly pigmented patients or those with RPE atrophy.

Figure 176-4 Vortex veins.

[edit] PHYSIOLOGY

The sensory function of the eye is performed by the neurosensory retina. The eye is capable of photopic and scotopic vision. Photopic vision is used in bright illumination and includes the recognition of colors; it is a function of the cone photoreceptors. Scotopic vision is used in dim illumination and does not include color recognition; it is a function of the rod photoreceptors. Cone photoreceptors are located primarily within the macula; rod photoreceptors are located in the peripheral retina. The macula therefore provides color vision as well as central visual acuity; the peripheral retina is responsible for peripheral vision and night vision.

The photoreceptors are located in the deepest portion of the retina. They contain light-sensitive pigment molecules in the 11-cis-retinal configuration. Once stimulated, they convert to the trans configuration, which initiates an electrical potential that spreads from the photoreceptor cell to the bipolar cell. The bipolar cells stimulate the ganglion cells, the axons of which form the nerve fiber layer. This nerve fiber layer exits the eye as the optic nerve. The optic nerve transmits the visual information back to the brain. The information that began at the photoreceptors ultimately ends in the visual cortex of the occipital lobe (see Fig. 176-2).

[edit] PATIENT EVALUATION

[edit] History

Specific symptoms, including painless visual disturbances, indicate retinal pathology (Table 176-1). Disorders of the peripheral retina impair peripheral vision and night vision. Disorders of the central retina affect central visual acuity and color vision. Decreased visual acuity suggests an abnormality within the macula or a media opacity (e.g., hemorrhage, inflammation) that is obscuring the macula. Abnormal color vision also may be associated with retinal disease. Congenital color defects may indicate cone photoreceptor abnormalities; acquired color defects may result from acquired macular disease. Unilateral peripheral field loss suggests peripheral retinal disease. Poor night vision may indicate rod photoreceptor dysfunction or generalized peripheral retinal disease. Entopsias (floaters) usually represent vitreous opacities. Photopsias (flashes) that are unilateral usually indicate retinal irritation. Causes of unilateral photopsia include vitreous traction, retinal detachment, and retinal or choroidal inflammation or infection. Metamorphopsia, including micropsia and macropsia, usually indicates macular dysfunction. Finally, monocular diplopia (double vision with one eye closed) also suggests macular dysfunction.

Table 176-1 Ocular Symptoms and Associated Retinal Disorders

[edit] Physical Examination

Media opacities in the vitreous cavity can be visualized by the direct ophthalmoscope. Retroillumination of the fundus reveals dark opacities within the red reflex. A dull or absent red reflex may indicate a retinal detachment, vitreous opacity, or intraocular tumor (Fig. 176-5).

Figure 176-5 Abnormal red reflex.

Abnormalities in the retina or choroid may be differentiated by the color of the lesions. Most abnormalities are red, yellow, white, gray-white, brown, or black (Box 176-1). Red lesions in the retina typically represent hemorrhage. The location of the hemorrhage, both topographically on the retina and depth within the retina, helps narrow the differential diagnosis. For example, a sector of retina with hemorrhages may contain a branch vein occlusion, whereas midperipheral and macular hemorrhages suggest a systemic vasculopathy such as hypertensive or diabetic retinopathy. In addition, the depth of the hemorrhages suggests different entities. An intraretinal hemorrhage is characteristic of diabetic retinopathy, whereas a subretinal hemorrhage is classic for a choroidal neovascular membrane. Vascular tumors (e.g., hemangiomas) and vascular abnormalities (e.g., telangiectasias) also appear red.

The most common yellow lesions are probably the deep subretinal lesions known as drusen ("bumps"). Seen in elderly patients, drusen are a risk factor in the development of age-related macular degeneration. Hard exudates also are a common yellow lesion seen in the retina. They have numerous causes, but the common pathophysiology is the presence of incompetent vasculature, which allows the exudation of extracellular material into the outer plexiform layer of the retina. Because the outer plexiform layer forms a radiating pattern from the central foveola, lipid exudates may form a so-called macular star if the incompetent vessels are located close to the macula. Atrophic chorioretinal scars also may appear yellow. Finally, heredodegenerative conditions may present with retinal or subretinal yellow lesions within the macula, periphery, or both.

White lesions include soft exudates, or cotton-wool spots. These focal areas of retinal ischemia block the retrograde axoplasmic flow, resulting in accumulation of axoplasmic material. Cotton-wool spots suggest different diagnoses but are not a diagnosis. They usually occur in retinal diseases characterized by retinal ischemia. Another white lesion consists of myelinated nerve fibers, are usually adjacent to the optic nerve and with feathering borders. Although they may be confused with cotton-wool spots, these lesions are whiter and persistent rather than transitory. Colobomas, which are a congenital absence of retinal and choroidal structures, also appear as white lesions. Fibrosis, which occurs with disciform scars, causes a white-appearing retinal lesion. Gliosis also can appear white and is impossible to differentiate from fibrosis without histology. Tumors such as astrocytic hamartomas and retinoblastomas can appear white. Finally, infectious retinitis or chorioretinitis can lead to the accumulation of inflammatory cells, which can give the retina a whitish appearance.

Gray-white lesions of the retina occur with edema or elevation of the retina. These lesions are usually associated with loss of the choroidal details. A retinal arterial occlusion can cause edema of the retina with a resultant gray-white discoloration. In addition, vascular leakage (e.g., diabetic maculopathy, retinal telangiectasia) can cause edema of the retina before the development of lipid exudation. Elevation of the retina can occur with retinal detachment from a tractional, rhegmatogenous, or exudative cause. Any of these etiologies of retinal detachment can cause the retina to appear gray-white.

Brown and black lesions indicate alterations in the pigment of the retina and choroid. Normally, pigment is seen only in the RPE and the choroidal stroma. Migration of pigment into the retina can occur with hereditary conditions such as retinitis pigmentosa. Migration also can be caused by retinal trauma or intraocular inflammation. Chorioretinal scarring can result in RPE hyperplasia, which appears as irregular brown-black lesions in areas usually with adjacent atrophy. Well-demarcated areas of black pigmentation usually signify congenital RPE hypertrophy. When pigmented lesions occur within the choroid, the lesions may have a subtle greenish hue. The most common lesion is a choroidal nevus. Another serious lesion is a choroidal melanoma, which is also elevated.

The retina and choroid respond in only a few ways to different pathologic insults. These signs, however, may vary considerably in their location, duration, fluctuation, and associated history.

[edit] VITREOUS ABNORMALITIES

The vitreous body is normally attached to the retinal surface early in life. The consistency of the vitreous changes from gel-like to liquid with age (Box 176-2). As this change occurs, condensations of collagen can present to the patient as floaters. These structures may be described as hairlike or cobweb shaped. They also may appear to the patient as insectlike. Floaters, although annoying, are not a threat to vision. With increasing liquefaction, liquid vitreous may insinuate between the posterior vitreous surface and the inner retinal surface, a condition known as a posterior vitreous detachment. An acute presentation is associated with photopsias. As the vitreous surface separates from the retina, the stimulated retinal surface produces the sensation of flashing lights. As the separating vitreous moves anteriorly, the collagen fibers condense even further, producing a more noticeable vitreous floater. A vitreous detachment alone is not a visual risk, but because vitreous detachments can be associated with retinal tears and vitreous hemorrhage, a referral within a week is warranted.

Vitreous detachments can be associated with vitreous hemorrhage when the retina or superficial retinal vessel is torn. More common causes of vitreous hemorrhage include diabetic proliferative disease and sickle cell disease. The bleeding comes from active neovascular tufts on the retinal surface. The patient presents with painless loss of vision. Initially the patient sees numerous floaters and may see a "waterfall," representing a stream of blood. The blood would then clot, and the patient may see a cobweb or a dense floater if the bleeding is not excessive. With a large amount of blood the complaint may be acute loss of vision. The patient should avoid aspirin and aspirin-like medicines, remain in a strict head-up position, and sleep with the head elevated at least 45 degrees to allow the blood to settle in the inferior vitreous cavity. A retinal specialist should be consulted within 24 hours.

Floaters and loss of vision also may be associated with vitritis, an inflammation of the vitreous. The inflammation spills into the vitreous from either the retina or posterior uvea (choroid or ciliary body). Any infectious or noninfectious inflammation of the choroid or retina produces similar symptoms. Generally, this posterior inflammation does not produce pain, and the eye also does not look inflamed. The red reflex is dulled, and ophthalmoscopy reveals obscured or absent details. Vitritis associated with recent ocular surgery may indicate bacterial endophthalmitis and warrants immediate referral to an ophthalmologist (Fig. 176-6). Vitritis not associated with previous ocular surgery may be referred to the ophthalmologist within 24 hours.

Figure 176-6 Bacterial endophthalmitis.

Other, uncommon vitreous conditions include synchysis scintillans and asteroid hyalosis (Fig. 176-7). These two conditions are characterized by the presence of crystals within the vitreous cavity. Asteroid hyalosis is a primary condition that presents with calcium crystals in the vitreous cavity. Synchysis scintillans is a secondary condition in which previous vitreous hemorrhage results in the deposition of cholesterol crystals in the vitreous cavity.

Figure 176-7 Asteroid hyalosis.

[edit] VITREORETINAL INTERFACE ABNORMALITIES

The vitreoretinal interface may be the location or the cause of ocular pathology (Box 176-3). Vitreous separation is the primary cause for these abnormalities. In the process of posterior vitreous separation, areas of tight vitreoretinal adhesion may become sites of retinal tear formation (Fig. 176-8). The symptoms of tears are not different from symptoms of posterior vitreous separation. Floaters and photopsias are often noted. Decreased vision related to vitreous hemorrhage also may be present. Since retinal tears may cause retinal detachment, patients with such symptoms should be seen within 24 hours.

Figure 176-8 Retinal tear.

Vitreous separation may also cause epiretinal membranes. The separation of the posterior hyaloid may cause microscopic dehiscence of the retinal internal limiting membrane. This dehiscense may give glial cells, metaplastic RPE cells, and fibrocytes access to the inner surface of the internal limiting membrane. The growth and ultimate contraction of this tissue result in distortion of the retinal surface (Fig. 176-9). Patients may complain of decreased vision and metamorphopsia. These complaints are chronic because the epiretinal membranes are slow growing. Visual impairment may be mild. If the visual acuity is better than 20/60 Snellen visual acuity, intervention is not warranted. For vision worse then 20/60, pars plana vitrectomy with removal of the epiretinal membrane is recommended. Because the progression of epiretinal membranes is slow and because many patients do not have significant visual impairment, the referral is not urgent. An appointment within 3 weeks is reasonable.

Figure 176-9 Epiretinal membrane.

When vitreous liquefaction causes retention of posterior cortical vitreous, this layer may exert horizontal traction on the retina. This horizontal or tangential traction may cause a full-thickness foveal dehiscence called a macular hole (Fig. 176-10). The formation of a macular hole may be associated with a rapid drop in visual acuity, which may not be appreciated by the patient because vision in the other eye remains good. On discovering the affected eye, the patient will notice a central scotoma with poor acuity. Certain macular holes may be treated surgically to remove the posterior cortical vitreous. Since this procedure can be attempted even years after the formation of a macular hole, an ophthalmic referral is not urgent. Consultation within 3 weeks is appropriate.

Figure 176-10 Macular hole.

[edit] RETINAL ABNORMALITIES

[edit] Vascular Disorders

Systemic hypertension can cause ocular changes that primarily affect the neurosensory retina (Box 176-4). Fundus examination may reveal focal or generalized attenuation of the retinal arterioles. Breakdown of the endothelial tight junctions may result in intraretinal hemorrhages and exudation. Hard exudates may be seen within the neurosensory retina. In severe cases these hard exudates may form a star within the macula. Focal areas of retinal ischemia may be seen as cotton-wool spots. Severe hypertension also may cause edema of the optic nerve. Recognition of hypertensive retinopathy may allow better control of hypertension and thereby lessen ocular complications (e.g., retinal vascular occlusions) and systemic complications (e.g., coronary artery disease, neurologic disease). The primary goal after diagnosis of hypertensive retinopathy is control of blood pressure. Once this is established, an ophthalmic referral may be made to rule out ocular complications.

Diabetic retinopathy has many of the retinal findings seen in hypertensive retinopathy because both cause similar breakdown in the vascular endothelial tight junctions. Intraretinal hemorrhages, hard exudates, cotton-wool spots, and microaneurysms may be seen on fundus examination. These findings indicate background diabetic retinopathy (BDR, Fig. 176-11). BDR is not a threat to vision except when retinal capillary ischemia or neurosensory retinal edema affects the fovea. In patients with foveal ischemia, vision is irreversibly damaged. Prevention of ischemia is the only approach. Tight control of blood glucose and blood pressure may prevent progression of ischemia. Neurosensory retinal edema, if located within 500 μ of the center of the foveal, is called clinically significant macular edema (CSME), and the patient is at risk for losing vision. This risk can be decreased by applying laser photocoagulation to the areas of retinal edema. Resolution of edema may take 3 to 4 months. If residual edema is present after this time, additional photocoagulation may be performed. With worsening retinal ischemia, growth of neovascular tissue can be seen on the optic nerve or elsewhere on the retina; this clinical picture is known as proliferative diabetic retinopathy (PDR, Fig. 176-12). Because bleeding may occur from these neovascular fronds, recognition of such vessels by the physician should be followed by prompt referral within 24 hours; otherwise, referral within 3 weeks is appropriate. Bleeding from neovascular fronds and formation of tractional bands that emanate from neovascular fronds cause decreased vision in patients with PDR. Patients with any three of the following four conditions are at high risk of losing vision and should be treated with panretinal laser photocoagulation: (1) any neovascular frond, (2) frond within 1 DD of the optic nerve, (3) large frond (large defined as ½ disc diameter if it is within 1 disc diameter of the optic nerve or greater than ½ disc diameter if elsewhere), and (4) associated vitreous or preretinal hemorrhage. If vitreous hemorrhaging does not clear, pars plana vitrectomy can be performed to clear the vitreous cavity. The time to wait before proceeding to vitrectomy is 2 months in type I and 4 months in type II diabetic patients. Vitrectomy can also be performed in diabetic patients who develop tractional retinal elevation that involves the fovea. Sickle cell disease can also be associated with neovascular fronds.

Figure 176-11 Background diabetic retinopathy.

Figure 176-12 Proliferative diabetic retinopathy. Note new vessels on optic nerve and peripheral laser scars.

Retinal venous occlusion can occur in either the central retinal vein or one of its branches (Figs. 176-13 and 176-14). If the fovea is involved, the patient presents with acute visual loss. Funduscopic examination reveals venous dilation, tortuous retinal veins, intraretinal hemorrhages, hard exudates, and cotton-wool spots in the affected quadrants. If the fovea is not involved, the patient may be asymptomatic or may present with only peripheral visual field loss. This diagnosis does not require acute intervention, but referral should be made within 24 hours to confirm the diagnosis.

Figure 176-13 Branch retinal vein occlusion.

Figure 176-14 Central retinal vein occlusion.

Retinal arterial occlusions also may occur within the central retinal artery or any of its branches. Arterial occlusion manifests as an ischemic, opaque retina in the affected quadrants, which may be associated with visible emboli within the arterial circulation and a cherry-red spot, or prominent red color in the fovea (Fig. 176-15). If the fovea is involved, vision drops acutely, creating one of the few extreme emergencies in ophthalmic practice. Once this diagnosis is suspected, the patient should be referred immediately to the ophthalmic specialist. A delay of even a few minutes may adversely affect visual outcome.

Figure 176-15 Central retinal artery occlusion. Note macular whitening with center cherry-red spot.

[edit] Retinal Pigment Epithelial Disorders

Two conditions of the RPE are central serous retinopathy and age-related macular degeneration. Central serous retinopathy generally occurs in patients less than 50 years of age, whereas macular degeneration occurs in older patients. The pathogenesis of central serous retinopathy probably involves misdirected fluid transport by the RPE. The epithelium transports fluid underneath the neurosensory retina, causing a neurosensory retinal elevation. The patient complains of acute loss of vision with metamorphopsia, usually micropsia. Examination of the fundus reveals a dulled foveal reflex and neurosensory retinal elevation. This condition is generally self-limited; within 4 months the neurosensory elevation resolves. If not, laser photocoagulation may be necessary. Referral can be made within 3 weeks.

Dry macular degeneration results from loss of RPE cells, giving the macula a mottled appearance (Fig. 176-16). The RPE has atrophic as well as hypertrophic regions. Subretinal accumulations of waste products (drusen) are yellow-white and primarily occur in the macula. Dry macular degeneration causes gradual central visual loss and has no definitive treatment at this time. Some speculate that exposure to visible and ultraviolet light may lead to formation of reactive oxygen species in the outer retina or choroid. This presumably could lead to dysfunction of the photoreceptor-RPE-choriocapillaris complex and hasten macular degeneration, which has led some to advocate use of antioxidants. Results of studies are inconclusive, but wearing sunglasses is encouraged. The role of diet and nutritional supplementation in managing patients with macular degeneration is not clear. The Age-Related Eye Disease Study (AREDS) may be able to answer these questions. Until then, a well-balanced diet and daily multivitamins are recommended for patients with macular degeneration.

Figure 176-16 Dry macular degeneration.

In 10% of patients with macular degeneration, new vessels grow underneath the retina. These abnormal extensions of choroidal vasculature are called choroidal neovascular membranes (CNVMs). These new vessels change the diagnosis from dry macular degeneration to wet-macular degeneration. The vessels have a propensity to grow close to the fovea and predispose the eye to subretinal exudation and subretinal hemorrhage (Fig. 176-17), both of which can cause rapid decrease in central visual acuity with accompanying metamorphopsia. If CNVMs are not immediately under the fovea, laser photocoagulation may allow closure of the vessels with retention of good visual acuity. Because the vessels show continued growth without treatment, urgent referral within 24 hours is mandated. CNVMs are visualized using intravenous fluorescein angiography (IVFA). This allows localization of the neovascular complex; the location in relation to the fovea is important to determine the available management options. If the CNVM is not under the fovea, laser photocoagulation is the best option, obliterating the CNVM with thermal energy. The effectiveness of therapy is determined by repeating IVFA 10 to 14 days after treatment. Any residual CNVM is re-treated with photocoagulation. Patients with CVNMs under the fovea are at risk for losing vision after laser photocoagulation. In select patients (smaller CNVM, worse starting vision), laser photocoagulation is still the preferred treatment modality. When the subfoveal CNVM is associated with moderately good vision, observation or photocoagulation that spares the fovea may be recommended. Other modalities being investigated for use in patients with subfoveal CNVM include photodynamic therapy using photosensitive dyes and surgical extraction of the CNVM using pars plana vitrectomy and subretinal surgery.

Figure 176-17 Wet macular degeneration. Note subretinal hemorrhage and subretinal scar.

[edit] Inflammatory Conditions

Retinal inflammatory conditions affect the RPE or inner retina and include retinal pigment epitheliitis, acute posterior multifocal placoid pigment epitheliopathy (Fig. 176-18), multiple evanescent white-dot syndrome, acute macular neuroretinopathy, and birdshot chorioretinopathy. These conditions primarily are acute in onset and occur in younger patients. The etiologies are presumed to be viral. They are usually self-limiting, and treatment is not warranted. Referral is semiurgent, with no immediate therapy necessary. Patients have acute loss of vision, and the affected eyes display yellow inflammatory lesions.

Figure 176-18 Acute multifocal placoid pigment epitheliopathy.

[edit] Infectious Conditions

Agents that infect the retina include the parasites Toxoplasma gondii and Toxocara canis as well as human immunodeficiency virus (HIV) and cytomegalovirus (CMV). Toxoplasmosis is acquired congenitally and results in large, bilateral, pigmented and depigmented chorioretinal scars, which contain the dormant organism that may reactivate later in adolescence or young adulthood. Reactivation results in marked retinal and vitreous inflammation and causes floaters and decreased vision. Toxocariasis also occurs in younger children and results in granuloma formation, primarily affecting the optic nerve, macula, or peripheral retina. The granulomas that affect the optic nerve and the macula usually are associated with decreased vision and a white pupillary reflex. They may result in retinal detachment and significant vitreal inflammation.

Viruses also may result in infectious retinitis. HIV may lead to formation of cotton-wool spots in the retina, which are white with soft margins. Cotton-wool spots are transitory and are not associated with a decrease in vision. When HIV-positive patients present with a white retinal lesion, the most devastating etiology is CMV retinitis, which initially may be indistinguishable from a cotton-wool spot. With time, the retinitis, which begins around retinal arterioles, acquires a cheeselike consistency and becomes associated with intraretinal hemorrhages (Fig. 176-19). The retinitis spreads rapidly and, if it involves the optic nerve or macula, is associated with sudden visual loss. HIV retinopathy necessitates every 2-to 3-month examinations for the detection of CMV retinitis. Once CMV retinitis is diagnosed, the patient needs lifelong treatment with ganciclovir, foscarnet, or a combination of the two. When CMV retinitis is suspected, immediate referral for confirmation is necessary.

Figure 176-19 Cytomegalovirus (CMV) retinitis.

[edit] Neoplastic Conditions

Retinal neoplasms may be pedunculated or sessile. The shape, color, and associated findings may help differentiate them. Because of its potentially fatal outcome, retinoblastoma should be ruled out immediately. Retinoblastomas are pedunculated white vascular tumors that may grow into the vitreous cavity or outward toward the choroid. Retinoblastoma is the most common intraocular malignancy of childhood, diagnosed mainly between ages 12 and 18 months, when a young child presents with a white pupil (Fig. 176-20) or new onset of ocular misalignment (strabismus). Because of the risk of metastatic spread, the child should be referred immediately for the possibility of enucleation.

Figure 176-20 Leukokoria (leukocoria, cat's eye reflex).

Retinal astrocytomas may be mistaken for retinoblastomas. Astrocytomas are pedunculated white lesions that extend into the vitreous cavity. They are benign growths of glial astrocytes and are primarily avascular. They have a "mulberry" shape and may be unilateral or bilateral and multifocal. Patients with tuberous sclerosis and neurofibromatosis may manifest retinal astrocytomas, but this tumor is usually not associated with systemic syndrome.

Retinal capillary hemangiomas are pedunculated vascular lesions that begin as small, red intraretinal lesions. With time they grow and can be recognized by the presence of a feeding retinal vessel. These hemangiomas may result in bleeding, exudation, and tractional retinal detachment. They may occur as a part of the autosomal dominant von Hippel–Lindau syndrome or on a nonfamilial basis. Because the larger tumors are more difficult to treat, hemangiomas should be diagnosed when they are small and can be treated with laser photocoagulation or retinocryopexy.

Retinal cavernous hemangiomas are sessile lesions that appear as a "cluster of grapes" on the retinal surface. They may be associated with similar skin and central nervous system lesions. Unlike retinal capillary hemangiomas, these lesions do not exhibit marked hemorrhage or exudation.

Congenital RPE hypertrophy is a jet-black lesion with well-defined margins (Fig. 176-21). RPE hyperplasia is an acquired condition with a mottled appearance and results from inflammation, trauma, or vitreoretinal traction. With the exception of suspected retinoblastomas, retinal tumors can be seen on a nonurgent basis.

Figure 176-21 Congenital retinal pigment epithelial hypertrophy.

[edit] Hereditary Conditions

Three factors should be considered when a hereditary retinal condition is part of the differential diagnosis. First, the condition tends to occur in younger patients, with most entities manifesting changes in adolescence or young adulthood. Second, the condition is usually bilateral, with symmetric involvement. Third, the patient may have other affected family members, and a specific genetic transmission pattern may be discovered. These entities may affect primarily the periphery and result in decreased peripheral vision and night vision or may affect the macula and result in early central visual loss. The most common peripheral entity is retinitis pigmentosa, and the most common central entity is cone dystrophy.

[edit] Retinal Detachments

Three pathogenic mechanisms can result in the retina being elevated off the RPE: rhegmatogenous detachments result from a break in the retina, tractional detachments from tractional fibrosis within the vitreous cavity, and exudative detachments from exudation of fluid under the retina. Rhegmatogenous retinal detachments, the most common type, result from posterior vitreous separation (Figs. 176-22 and 176-23). The subsequent retinal break allows liquid vitreous to enter the subretinal space and cause a retinal detachment. The patient generally presents with photopsias and entopsias. With detachment of the fovea, central vision greatly decreases. When the fovea is not detached, central vision can be quite good, even though peripheral vision is limited. When a patient has symptoms of a detachment and good vision, the referral should be made urgently. If vision is decreased, the patient can be seen semiurgently. The primary goal should be to prevent foveal detachment. Once the fovea detaches, surgery to reattach the retina may be performed within a week for equivalent results.

Figure 176-22 Rhegmatogenous retinal detachment.

Figure 176-23 Vitreous detachment, retinal hole, and retinal detachment. A, Vitreous body has collapsed and pulled away from retina in posterior half of eye. Retina remains intact. B, Vitreous body has detached from retina in posterior portion of eye. Superiorly, strong adhesion between vitreous and retina remains, with retinal tearing caused by vitreous detachment. Retinal tear usually has "horseshoe" appearance when viewed through ophthalmoscope. C, Vitreous has detached as in A and B and has caused a retinal tear as in B. Fluid from area of liquid vitreous posteriorly has coursed through retinal hole, and retina has detached from eye wall, with a balloon shape on ophthalmoscopy.

The most common cause of tractional retinal detachment is diabetic retinopathy. The proliferative stage results in growth of vascular and fibrous components into the vitreous cavity. The fibrous component may cause tractional forces to develop between the retina and vitreous. These forces may cause the retina to be pulled off the underlying RPE. Unlike rhegmatogenous detachments, tractional detachments do not produce acute symptoms, and the earliest detectable symptom may be visual loss once the fovea detaches. Tractional detachments are slow to form, and thus referral is semiurgent. Treatment involves vitrectomy surgery to remove the tractional components; this procedure is performed only if the fovea is detached or if foveal detachment appears imminent.

Exudative retinal detachments result from subretinal inflammatory and neoplastic conditions that cause the accumulation of fluid under the retina. The fluid has the ability to "shift" under the retina, with different portions of the retina detaching with alterations in position. Once the fluid reaches the fovea, vision decreases. These detachments tend to be inferior in primary position because of gravity. Consultation should be urgent.

[edit] CHOROIDAL ABNORMALITIES

Choroidal neovascular membranes occur when normal choroidal vasculature extends into the subretinal space through breaks in Bruch's membrane (Box 176-5). Several conditions may result in such a break. Angioid streaks result in Bruch's membrane cracks that radiate from the optic nerve. These orange-red streaks may occur in patients with pseudoxanthoma elasticum, sickle cell disease, and Paget's disease. High myopia may result in attenuations of Bruch's membrane, or lacquer cracks, which occur primarily in the macula. Trauma can result in ruptures of the choroid, including Bruch's membrane. These ruptures usually occur concentrically around the optic nerve. Presumed ocular histoplasmosis syndrome results in circular, yellow-white chorioretinal scars. These scars have breaks in the overlying Bruch's membrane. All these conditions may result in green-gray extensions of the choriocapillaris under the retina, resulting in subretinal exudation and hemorrhage. Depending on the location of CNVMs, central visual acuity may be greatly affected. If no predisposing factor is present, the CNVM is considered idiopathic. Once the diagnosis is suspected, urgent referral is made for possible laser photocoagulation to obliterate the CNVM.

[edit] Inflammatory Conditions

As with retinal inflammatory conditions, choroidal inflammatory conditions have unknown etiologies. The entities are diagnosed because of the constellation of signs that accompany each disorder. All the choroidal inflammatory disorders may present with photopsias and decreased vision that is sudden in onset. Serpiginous choroidopathy occurs in a peripapillary location. The choroid is actively inflamed, and the leading edge has a snakelike shape. Multifocal choroiditis and punctate inner choroidopathy both have characteristic inflammatory inner choroidal lesions. The eye usually has lesions in different stages of evolution. The acute lesions have a yellowish, thickened appearance, whereas the chronic lesions resemble typical chorioretinal scars that are circular with pigmented and depigmented components. The difference between the two conditions is that multifocal choroiditis has intravitreal inflammation, whereas punctate inner choroidopathy does not.

[edit] Neoplastic Conditions

Choroidal neoplastic conditions present as melanotic or amelanotic, unifocal or multifocal subretinal lesions. The most common entity is the choroidal nevus (Fig. 176-24). This benign accumulation of melanocytic cells presents as a flat, greenish brown lesion. This congenital lesion may become more pigmented with time, and its size varies from less than 1 mm to many millimeters. The patient has no overlying retinal involvement and is asymptomatic. These patients should be referred semiurgently. Follow-up consists of yearly observation because of the small risk of malignant transformation into a malignant melanoma.

Figure 176-24 Choroidal nevus.

A choroidal malignant melanoma may arise from a choroidal nevus or may arise de novo (Fig. 176-25). Although amelanotic melanomas are present, the more common presentation is a melanotic subretinal lesion. The color may range from green to brown; a jet-black lesion is rare. A melanoma is differentiated from a nevus by its height (2 to 15 mm). Melanoma may be associated with neurosensory retinal elevation, subretinal exudation, and subretinal hemorrhage. Large melanomas can show extension through the sclera. Metastatic spread of a choroidal melanoma occurs primarily to the liver and lungs. Once metastasis occurs, life expectancy is less than 1 year. Treatments include observation, laser photocoagulation, cryopexy, radiation, surgical resection, or enucleation. Urgent referral while the tumor is still small may afford the patient and retina specialist more treatment options, which may save some sight as well as the patient's life.

Figure 176-25 Choroidal melanoma.

Another malignant condition of the choroid is metastatic disease. Choroidal metastases are primarily amelanotic, multifocal lesions that occur in the posterior pole and result in visual decline. Bilateral involvement is common. The condition affects men and women equally. The most common primary tumors are in the breasts and lungs; less common sites include the kidneys, testicle, prostate, and gastrointestinal tract. Ocular involvement may be the first sign of lung cancer, whereas patients with choroidal metastases from breast cancer usually have already been diagnosed. Although systemic treatment is essential in metastatic disease, ocular radiation may be beneficial in patients whose vision has decreased from choroidal metastases.

[edit] REFERRAL

Once symptoms implicate a possible abnormality in retinal or choroidal structures, examination can be directed appropriately. If a confident diagnosis can be made, referral should be made urgently or semiurgently. When the diagnosis cannot be made confidently, referral to the ophthalmologist should be made emergently, within minutes, if the symptoms are acute, or urgently, within 24 hours, if the symptoms are chronic.

[edit] ADDITIONAL READINGS

• American Academy of Ophthalmology: Basic and clinical science course, Section 4. Retina and vitreous San Francisco: The Academy; 1987:
• MD Davis: The natural history of retinal breaks without detachment. Trans Am Ophthalmol Soc 1973; 71:343.
• Diabetic Retinopathy Study Report Number 3: Four risk factors for severe visual loss in diabetic retinopathy. Arch Ophthalmol 1979; 97:658.
• Early Treatment Diabetic Retinopathy Study Report Number 2: Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Ophthalmology 1987; 94:761.
• Endophthalmitis Vitrectomy Study Group: Results of the Endophthalmitis Vitrectomy Study: a randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 1995; 113:113.
• GF Hilton, EB McLean, EL Chuang: Retinal detachment San Francisco: American Academy of Ophthalmology; 1989:
• RN Johnson, JD Gass: Idiopathic macular holes: observation, stages of formation, and implications for surgical intervention. Ophthalmology 1988; 95:917.
• R Klein, BEK Klein, KLP Linton: Prevalence of age-related maculopathy: the Beaver Dam Eye Study. Ophthalmology 1992; 99:933.
• Macular Photocoagulation Study Group Argon laser photocoagulation for neovascular maculopathy: five-year results from randomized clinical trials. Arch Ophthalmol 1991; 109:1109.
• AR Pilkerton, WS Gilbert, LE Perrant,et al.: Idiopathic preretinal fibrosis: a review of 237 cases. Ophthalmol Surg 1992; 23:113.
• AP Schachat, AF Cruess: Ophthalmology Baltimore: Williams & Wilkins; 1984:
• JA Shields: Counseling the patient with a posterior uveal melanoma. Am J Ophthalmol 1988; 106:88.