Chapter 133 – Angioid Streaks
JAMES F. VANDER
• Irregular, jagged breaks in an abnormal, calcified Bruch’s membrane.
• Narrow, jagged lines deep to the retina.
• Radiating out from the optic disc in a fashion similar to the retinal vessels.
• Choroidal neovascularization.
• Optic disc drusen.
• “Peau d’orange.”
• Retinal hemorrhages.
• Systemic diseases: pseudoxanthoma elasticum, Paget’s disease, sickle hemoglobinopathies.
Angioid streaks were initially reported in 1889 by Doyne, who described angioid streaks in a patient who had retinal hemorrhages secondary to trauma. Knapp first coined the term “angioid” streaks because their appearance suggested a vascular origin. Not until 1917 did Kofler correctly determine that angioid streaks represented changes at the level of Bruch’s membrane. Clinical examination with subsequent histopathological correlation later confirmed that the underlying abnormality was not vascular in nature but rather a structural alteration in Bruch’s membrane. 
EPIDEMIOLOGY AND PATHOGENESIS
Angioid streaks have been documented in early childhood but are not thought to be present at birth. Angioid streaks represent breaks or dehiscences in a thickened, calcified, and abnormally brittle Bruch’s membrane. Whether the breaks occur spontaneously or are caused only by trauma, even if minor, is not known. The initiating stimulation for the calcification and degeneration of Bruch’s membrane in patients who have angioid streaks is not yet known. No known sex or race predilection exists.
Angioid streaks appear as narrow, jagged lines deep to the retina, almost always bilaterally. They can closely resemble blood vessels because of their size, shape, color, and course ( Fig. 133-1 ). Angioid streaks typically radiate out in a cruciate pattern from an
Figure 133-1 Peripapillary angioid streaks. Classical ophthalmoscopic appearance associated with a choroidal neovascular membrane.
area of peripapillary pigment alterations, although they may circumferentially ring the peripapillary area as well. Generally, they taper and fade a few millimeters away from the optic disc; however, they have been reported to extend farther anteriorly.  Very rarely they occur in a random distribution throughout the posterior pole. The number of streaks can be variable. Progression of the streaks with time has been observed.
The color of angioid streaks depends on the background coloration of the fundus and the degree of atrophy of the overlying retinal pigment epithelium (RPE). In lightly colored fundi, angioid streaks are red, reflecting the pigmentation of the underlying choroid. In patients who have darker background pigmentation, angioid streaks are usually a medium to dark brown.    A gray color also occurs. The RPE on either side of an angioid streak often manifests pigment alterations as well. Some patients have mottled RPE, either locally or diffusely throughout the macular area; this is referred to as peau d’orange (“skin of an orange”; Fig. 133-2 ). Although most commonly seen with angioid streaks related to pseudoxanthoma elasticum, the peau d’orange fundus is also seen in patients who have other underlying systemic diseases.
The factors responsible for the characteristic radiating configuration of angioid streaks are not clear. It has been suggested that the pull of the extraocular muscles creates stress forces against the fixed point of the optic nerve, which results in the characteristic pattern.
Optic disc drusen have been associated with angioid streaks. As many as 25% of patients who have angioid streaks have clinical or echographic evidence of disc drusen.
Figure 133-2 Mottled pigmentation of the fundus, known as “peau d’orange.”
Although the diagnosis of angioid streaks is usually made on the basis of ophthalmoscopic observations, intravenous fluorescein angiography can help to delineate the presence of angioid streaks when the ophthalmoscopic appearance is subtle. With fluorescein angiography, angioid streaks are variably hyperfluorescent depending on the condition of the overlying RPE ( Fig. 133-3 ). Adjacent to the streaks, the RPE can be irregularly clumped, which results in a mottled appearance. When present, a choroidal neovascular membrane shows the classical increase in both size and intensity of the fluorescence as the angiogram progresses ( Figs. 133-4 and 133-5 ).
Indocyanine green (ICG) angiography shows hyperfluorescent lines that are larger and more numerous than those see on fluorescein angiography or red-free photography ( Fig. 133-6 ).  In some eyes with suspected choroidal neovascularization, ICG angiography demonstrates the membrane more clearly than fluorescein angiography.
The differential diagnosis consists of:
• Choroidal rupture
• Lacquer cracks
• Myopic degeneration
• Age-related macular degeneration
The most common systemic disease associated with angioid streaks is pseudoxanthoma elasticum. In one large series, approximately 50% of the patients who had angioid streaks also had pseudoxanthoma elasticum. Pseudoxanthoma elasticum is a systemic disease whose hallmark feature is abnormal skin and subcutaneous tissue, but the clinical spectrum may include arterial insufficiency secondary to calcification of blood vessels as well as gastrointestinal bleeding. The skin findings are classical and most commonly seen in the neck, axillary, inguinal, and periumbilical areas. They are said to resemble the skin of a plucked chicken ( Fig. 133-7 ). No sex or race predilection exists, and both autosomal dominant and recessive inheritance modes have been described. A primary disorder of elastic tissue is the underlying pathophysiology.
Angioid streaks are seen in 80–87% of all patients who have pseudoxanthoma elasticum. Aside from angioid streaks, other
Figure 133-3 Fluorescein angiogram of the same patient as in Figure 133-1 . Hyperfluorescence of radiating angioid streaks, along with a well-defined choroidal neovascular membrane.
Figure 133-4 Fluorescein angiogram. Choroidal neovascularization is secondary to angioid streaks. The early transit phase demonstrates hyperfluorescence at the level of pigment epithelium.
associated ocular findings with pseudoxanthoma elasticum include peau d’orange, as described earlier, and “punched out” peripheral chorioretinal lesions, similar to those seen with presumed ocular histoplasmosis.
Of patients who have Paget’s disease of bone (osteitis deformans), 2–15% have angioid streaks as well.  Paget’s disease is characterized by heavy calcification of bones. The pelvis, skull, femur, and humerus are most commonly affected. The underlying pathogenesis is an exuberant osteoclastic reaction with a secondary osteoblastic response. Some evidence exists that a slow virus is responsible. Diagnosis is made most readily on the basis of an elevated serum alkaline phosphatase level, with confirmation using radiography or a bone scan.
Patients who have sickle cell disease and other hemoglobinopathies can develop angioid streaks. Various studies have found the incidence to be in the range 0–6%. A strong correlation exists between age and the development of angioid streaks, which explains why studies that have looked at patients who have sickle disease, most of whom are younger than 40 years, show a low incidence of angioid streaks. Angioid streaks are rarely seen in patients younger than 25 years.
Many other systemic diseases have been linked to the presence of angioid streaks ( Box 133-1 ); some of these associations
Figure 133-5 Late phase angiogram of the same patient as in Figure 133-4 . Leaking hyperfluorescence typical of choroidal neovascularization is seen.
Figure 133-6 An indocyanine green angiogram of choroidal neovascularization secondary to angioid streaks. The streaks are starkly hyperfluorescent.
may represent coincidental occurrences. Because angioid streaks are often an acquired manifestation of systemic disease, studies that attempt to document population prevalences are strongly age dependent. Work-up for systemic disease in patients with angioid streaks should include skin biopsy, serum alkaline phosphatase, serum calcium and phosphate, and hemoglobin electrophoresis. About 40% of all patients who have angioid streaks do not have an underlying, causative systemic problem.
The elastic lamina that occupies the midsegment of Bruch’s membrane is primarily affected, which results in disintegration and fraying of the elastic fibers ( Fig. 133-8 ). Diffuse and extensive basophilic stains caused by the deposition of calcium are commonly seen with routine hematoxylin and eosin. The choriocapillaris and RPE are minimally affected initially; however, with progression these structures become secondarily degenerated. Eventually, neovascular vessels from the choroid may penetrate through the breaks in Bruch’s membrane, which results in subretinal hemorrhage, exudation, and edema followed by the fibrovascular deposition that is typical of a disciform scar. All cases of angioid streaks studied histopathologically have
Figure 133-7 Plucked chicken skin appearance on neck is characteristic of pseudoxanthoma elasticum.
Systemic Conditions Associated with Angioid Streaks
Hemolytic anemia (acquired)
Paget’s disease of bone
Sickle cell disease/hemoglobinopathies
shown identical changes despite different underlying systemic diseases.
TREATMENT, COURSE, AND OUTCOME
Because angioid streaks are generally asymptomatic and not visually significant, no treatment is warranted. Patients who have angioid streaks should be advised to avoid activities that increase the likelihood of a blow to the eye because of the increased risk of subretinal hemorrhage from relatively minor trauma.
If a choroidal neovascular membrane develops with secondary serous or hemorrhagic detachment of the retina, laser photocoagulation should be considered. The efficacy of photocoagulation for choroidal neovascularization has not been the subject of controlled, clinical trials. Some evidence exists that laser photocoagulation for well-defined extrafoveal or juxtafoveal membranes is beneficial. Singerman and Hatem reported long-term successful
Figure 133-8 Angioid streaks. A, This patient with angioid streaks also had pseudoxanthoma elasticum. Breaks in Bruch’s membrane around the optic nerve resulted in angioid streaks. B, Similar breaks away from the optic nerve have resulted in “peau d’orange” appearance (a, angioid streaks; p, peau d’orange). The yellow area just temporal to the optic nerve represents subretinal neovascularization. C, A histologic section of another case, from a patient with Paget’s disease, also shows streaks caused by an interruption (break) in Bruch’s membrane. (From Yanoff M, Fine BS. Ocular pathology, ed 5. Philadelphia: WB Saunders; 2002.)
treatment with seven out of eight membranes. A subsequent study of 30 eyes treated using light photocoagulation showed that the vision remained stable or was improved in 16 eyes and that vision in 14 eyes worsened, although 12 of the patients concerned retained 20/200 visual acuity or better. In a group of patients with 11 untreated eyes showing subretinal neovascularization, all had the visual acuity of counting fingers. Lim et al. found either recurrence or persistence of 14 out of 24 well-defined choroidal neovascular membranes. The presence of a disciform scar or choroidal neovascularization in the fellow eye is a poor prognostic factor for successful laser treatment. Repeated treatment may be necessary, as the recurrence rate appears to be high. No role exists for prophylactic photocoagulation of angioid streaks.
Photodynamic therapy is a technique for treatment of subfoveal choroidal neovascularization using a photosensitizing intravenous dye followed by low-energy infrared laser. Initially approved for use in age-related macular degeneration, photodynamic therapy has been shown to have some promise in treatment of subfoveal neovascularization in angioid streaks.
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