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Angioid Streaks

Editor: Jessilin M. Quint Updated: 11/13/2023 10:35:12 AM


Angioid streaks are breaks in the degenerated and mineralized Bruch membrane, first described by Doyne RW in 1889.[1] Angioid streaks have also been called Knapp streaks or Knapp striae in honor of the famous German-American ophthalmologist Jacob Hermann Knapp (1832–1911), who used the term "angioid streak" for the first time.[1] These typically form around the optic disc and radiate from the optic disc and are usually linear and hence named angioid or like blood vessels. Angioid streaks may be idiopathic or associated with pseudoxanthoma elasticum, Sickle cell disease, acromegaly, Paget disease of the bone, and other diseases. The angioid streak may be associated with choroidal neovascularization (CNV), causing metamorphosis and/or visual decline. Patients with angioid streaks are at risk for subretinal bleeding after minor trauma.[2] 


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This condition's most crucial systemic association is pseudoxanthoma elasticum (PXE) or Grönblad–Strandberg syndrome, an autosomal recessive disease caused by the mutation of the ABCC6 gene on chromosome 16.[3][4] The syndrome's name comes from Ester Elisabeth Grönblad (1898-1942), a Swedish ophthalmologist, and James V Victor Strandberg (1883-1942), a Swedish dermatologist who discussed the association between eye and skin findings in PXE. Features of this condition include calcification and fragmentation of elastic tissues. However, Angioid streaks may be idiopathic in up to 50% of cases.[1]

PXE is characterized by:

  • Skin lesions (discrete in early-stage and later confluent yellowish papules or pseudoxanthomas) at the sides of the neck, umbilical region, and flexures like the elbow with a "plucked chicken" appearance [5]
  • Gastrointestinal bleeding
  • Intermittent claudication/peripheral arterial vascular disease
  • Coronary artery disease
  • Aneurysms at the brain, kidney, and mesentery may cause hemorrhage [6]
  • Brain infarct or hemorrhage [3] 

Ocular manifestations include the following:

    • Appearance of Peau d'orange color of the fundus in children previous to angioid streaks.
    • Nearly all patients with PXE show angioid streaks 20 years after the first diagnosis.
    • Ultrasound detection of optic nerve head drusen was found in 25% of cases with angioid streaks.[7]
    • Pattern dystrophy of the macula
      • In a study on 22 confirmed cases of PXE, 27 eyes of 16 patients had pattern dystrophy.[8] All 5 variants of pattern dystrophy were reported in these cases, including fundus pulverulentus, butterfly-shaped dystrophy, fundus flavimaculatus, reticular dystrophy, and vitelliform pattern dystrophy.[8] Fundus fluorescein angiogram (FFA) helps to differentiate various pattern dystrophies. The type of pattern dystrophy may change with time, and the changes may appear on follow-up.
    • Small round retinal pigment epithelial (RPE) atrophic patches that may have a white, yellow, or pink color. Also may be seen are punched-out scars similar to presumed ocular histoplasmosis syndrome (POHS); these scars have been called "salmon spots."
    • Crystalline bodies or whitish subretinal round lesions in the mid-peripheral fundus, usually inferiorly. Some of these nodules have a comet-like tail of depigmentation. Up to 75% of cases show a crystalline body.
    • Atrophy of retinal pigment epithelium (RPE) near the angioid streak

Characters of acute retinopathy of PXE are:

  • Symptoms of unilateral visual decline, metamorphopsia, glare, relative scotoma, scintillations, and flashes.[9] 
  • Vitreous cells are usually present.
  • Outer retinal white dots are noted, usually around the optic disc. These dots are confluent around the angioid streaks, large vessels, and the optic nerve head. These are hyper-autofluorescent. The features are similar to multiple evanescent white dot syndrome (MEWDS), suggesting possible autoimmune pathogenesis.[9] 
  • Optical coherence tomography (OCT) features include loss of ellipsoid zone and interdigitation zone, subretinal hyperreflective lesion along angioid streaks that appear similar to choroidal neovascular but without subretinal hemorrhage, and subretinal or intraretinal fluid or leakage on fluorescein angiogram.
  • Indocyanine green angiogram shows hypocyanescent lesions that become more prominent after 30 minutes. The options for managing this condition are still being explored and include systemic steroids and intravitreal anti-vascular endothelial growth factor agents if hyperreflective material is noted subretinally on OCT. Though visual recovery to normal vision is possible, some cases have irreversible visual decline.[9] Acute retinopathy may recur and simulate punctate inner choroidopathy or idiopathic multifocal choroiditis.[10]

Other associations of angioid streaks include the following:

  • Marfan syndrome
  • Paget disease of bone
    •  Up to 10% of cases have angioid streak noted.[11]
  • Sickle cell disease 
    • Angioid streak is found in around 1% to 2% of cases, usually after the third decade. Sickle cell trait, homozygous sickle cell disease, sickle cell thalassemia, and sickle cell hemoglobin C disease have also reported angioid streaks. 
  • Other hemoglobinopathies
    • Acquired hemolytic anemia, hereditary spherocytosis, beta thalassemia major, beta thalassemia minor, beta thalassemia intermedia, hemoglobin H disease, and congenital dyserythropoietic anemia type 1.
  • Acromegaly
  • Hemochromatosis
  • Diabetes mellitus
  • Sturge Weber syndrome with facial angiomatosis
  • Myopia [12]
  • Hyperphosphatemia [12]
  • Neurofibromatosis [12]
  • Hypercalcemia
  • Abetalipoproteinemia
  • Familial polyposis of the colon
  • Congenital hypertrophy of retinal pigment epithelium
  • Diffuse lipomatosis [1]
  • Cutaneous calcinosis
  • Microsomia
  • Myopia [1]
  • Trauma [1]
  • Hypertensive coronary disease [1]
  • Senile elastosis
  • Epilepsy
  • Diabetes mellitus [12]


The age of presentation to the ophthalmologist is variable. Most commonly, patients with angioid streaks present at around 55 years but may present at a younger age if comorbidities are present. Central visual loss is mainly related to foveal involvement with dehiscence of the Bruch membrane or neovascular membrane. Choroidal neovascularization is a common cause of vision loss and affects most patients with angioid streaks. No predilection to gender is described. White individuals are usually affected most.[1][13]


The orientation of angioid streaks may be related to force lines due to the pull of intrinsic and extrinsic muscles of the eye around a fixed location (eg, optic nerve). The fragility and opacification of Bruch membrane may be primarily due to the degeneration of the elastic portion of Bruch membrane along with the deposition of calcium, magnesium, or iron salts from disturbed metabolism.[14]


Degradation and mineralization of the tissues containing elastin and/or collagen characterize PXE. The Bruch membrane is hard yet fragile in PXE due to calcification.

The histopathological examination of the angioid streak reveals:

  • Thickening and mineralization (calcification) of the Bruch membrane [12]
  • Crack-like, well-demarcated dehiscence of the Bruch membrane at the collagenous and elastic region 
  • A fibrovascular or neovascular tissue may form at the edge of the dehiscence of Bruch membrane and grow under the retina or RPE

History and Physical

Angioid streaks are usually asymptomatic visually. The visual decline may result from foveal involvement with an angioid streak, rupture at the area of the angioid streak causing subretinal bleed at the fovea, or CNV. These hemorrhages do not have evidence of CNV and usually resolve spontaneously. However, the angioid streak may be associated with CNV, which may cause visual decline and/or metamorphopsia.

Patients with PXE may be referred from the dermatology department for ophthalmic evaluation, leading to the diagnosis of angioid streaks. According to the disease, other systemic associations will have history and clinical examination findings. The patient history should try to rule out systemic association.

Clinical Features

Perform a comprehensive ocular examination with the inclusion of visual acuity, refraction, intraocular pressure, ocular motility, the examination of the ocular adnexa, lacrimal system, cornea, anterior chamber, iris, pupillary reaction including a relative afferent pupillary defect,[15] lens, and fundus.

Clinically, angioid streaks (see Image 1. Fundus With Angioid Streaks) are characterized by:

  • Jagged irregular lines approximately of the caliber of a retinal vessel radiating from the optic disc
  • Serrated margins of the streaks 
  • Variable caliber (50–500 µm)
  • Subretinal location (the retinal vessels are superficial to the angioid streaks)
  • Streaks that may be interconnected at places (usually forming a ring around the optic disc).
  • Gray, black, reddish, or pink color, depending on the pigmentation of the choroid visible through the thin RPE and gap in the Bruch membrane
  • The tendency to involve the macula
  • Usually located behind the equator
  • Abrupt tapering at the end away from the optic disc (towards the peripheral retina)
  • In eyes with media haze, the angioid streak may be subtle and overlooked.
  • The angioid streak may be confused with retinal blood vessels on cursory examination.
  • With age, the number, width, and length of angioid streaks may increase.
  • Usually, angioid streaks are bilateral; however, the fundus changes may be asymmetric.
  • Some cases may have equally spread depigmentation around the angioid streak, which can be on either side. The width of this depigmented area may vary, extending up to 3 times the width of the angioid streak on either side.[16]

 Associated features include:

  • Peau d'orange appearance of the fundus (see Image 2. Angioid Streak, Glaucomatous Optic Nerve, and Choroidal Neovascularization)
    • There is pigmentary mottling (small areas of pigmentation that are sometimes confluent at the level of retinal pigment epithelium interspersed with a normal fundus color), specifically temporal to the fovea, sometimes reaching the equator, giving an appearance of the skin of an orange. Rarely, the changes may be extensive, and retina nasal to the optic disc may also be involved. It is not as common in angioid streaks associated with sickle cell disease or Paget disease of the bone.
  • Optic disc drusen
    • The disc is hyperautofluorescent and shows a hyperechoic lesion with acoustic shadow on ultrasound of the optic nerve head.
  • Peripapillary chorioretinal degeneration
  • Macular thinning or pigmentary changes
    • The changes are usually bilateral, with no hemorrhage or hard exudates.
  • CNV or disciform scar (see Image 3. Angioid Streaks on Fundus.)
    • Usually, an associated angioid streak presents near the CNV. Subretinal fluid, hard exudates, or blood may characterize the CNV. The incidence of CNV in angioid streak may be up to 86%, and bilateral involvement is in up to 71% of cases.[1] Subretinal CNV (type 2) is usually seen. The CNV is usually recurrent. CNV causes poor vision in patients with angioid streaks, and vision loss occurs earlier than CNV due to wet age-related macular degeneratio. The chances of development of CNV are high if the angioid streaks are wide and long if they involve an area within 1 disc diameter of the foveola.[17] Cracked egg-shell appearance or diffuse type of angioid steaks also predispose CNV.[18] PXE has a higher risk of macular CNV.
  • Subretinal/submacular hemorrhage
    •  The patient usually presents with a visual decline due to subfoveal hemorrhage.
  • Peripheral chorioretinal scar
    •  This may simulate presumed ocular histoplasmosis syndrome (POHS).
  • Crystalline bodies and comet-shaped lesions
  • Pattern dystrophy of the macula
  • The end stage of the angioid streak is "disciform macular degeneration, helicoid peripapillary atrophy, or diffuse choroidal sclerosis with obscuration of the angioid streaks."[17]


Ocular Investigations

Infrared imaging may detect subtle angioid streaks missed in color fundus photos.[19]

Hypo-autofluorescence is in the area of the angioid streak, and the area of abnormality on autofluorescence may be larger than the abnormality visible in a color fundus photo or clinical examination.[1]

FFA usually shows window defects corresponding to the area of angioid streaks. FFA is essential to detect choroidal neovascularization.[20]

Optical coherence tomography (OCT) reveals the retinal/subretinal/sub-RPE changes in CNV and also hyper-reflectivity at the Bruch membrane level due to calcification. The en-face OCT may reveal the areas of angioid streaks. The choroid may be thinner in eyes with angioid streaks and CNV than those without CNV.[21]

OCT-angiogram may demonstrate the CNV in the angioid streak.

Indocyanine green angiogram (ICGA) may reveal a speckled pattern of cyanescence at the region of Peau d'orange appearance and reveal the CNV.[22] The angioid streaks may show hypercyanescene, hypocyanescence, or mixed pattern.[1]

Systemic Investigations

Evaluate patients with angioid streaks for systemic associations and perform related imaging and lab tests.

Treatment / Management

Angioid streaks are usually asymptomatic and do not need any treatment. However, eyes with angioid streaks are more prone to develop subretinal hemorrhage after trivial trauma, so advise patients to use protective eyewear.[2] All patients with angioid streaks should be screened for potential systemic associations. Examination of family members may give clues to the systemic disease. Perform a fundus fluorescein angiogram to rule out CNV in cases with subretinal hemorrhage.[20] If CNV is absent, the hemorrhage usually resolves independently.(B3)

If CNV is detected, the management options include laser photocoagulation, photodynamic therapy (PDT), transpupillary thermotherapy (TTT), macular translocation surgery, and anti-vascular endothelial growth factor (anti-VEGF) agents.[22] Recurrence of CNV causing vision loss is a concern in the angioid streak.

Among anti-VEGF agents, ranibizumab, aflibercept, and bevacizumab (off-label) have been used successfully and may improve or stabilize visual acuity. All anti-VEGF agents have efficacy against both macular and juxta-papillary CNV and may rapidly improve the retinal anatomy on OCT. Anti-VEGF agents may help stop the activity of CNV without forming a scar.[1] Anti-VEGF therapy improved visual acuity and central macular thickness in patients with CNV related to pattern dystrophy-like deposits in PXE.[23]

Differential Diagnosis

Differential diagnoses of angioid streaks include:

  • Normal retinal vessels
  • Lacquer cracks
    • Pathological myopia is noted in this degenerative finding, also characterized by breaks in the Bruch membrane. This condition may be associated with subretinal hemorrhage without evidence of CNV.
  • Reticular dystrophy of the retinal pigment epithelium (RPE)
    • RPE changes that cause pigmentation in the 'fishnet with knot' pattern characterize this condition. The changes are located at the posterior pole and may cause a circle similar to angioid streaks. 
  • Subretinal tracks due to ophthalmomyiasis interna are smooth and may cross each other multiple times.[24]
  • In long-standing retinal or operated retinal detachment cases, subretinal bands may be noted and simulate angioid streaks.
  • Wet age-related macular degeneration may cause bilateral disciform scars. 
  • Peripheral punched-out scars may simulate POHS.


The visual and long-term prognosis of both treated and untreated patients with choroidal neovascularization is generally poor.[25] A large study showed that the "ratio of central RPE atrophy enlargement" was 240% and 111% in the PDT and no PDT groups, respectively.[25] This study suggested the use PDT with caution in choroidal neovascularization associated with angioid streaks.[25] Systemically, most patients with pseudoxanthoma elasticum have an average life span; early death can occur due to gastrointestinal hemorrhage, cerebral hemorrhage, and myocardial infarction.


The complications of angioid streaks are:

  • Subretinal bleed due to choroidal rupture after trivial trauma [2]
  • Choroidal neovascularization [26] causes subretinal hemorrhage, intraretinal or subretinal hemorrhage, or exudate, often leading to a disciform scar that can cause severe vision loss, and early treatment with anti-VEGF usually stabilizes vision and may improve vision in some cases. Some patients with subretinal hemorrhage in angioid streaks may not have evidence of choroidal neovascularization [27]
  • Foveal atrophy/thinning

Deterrence and Patient Education

The patients should be informed about the potential risk of developing CNV. The Amsler chart helps in the home monitoring of metamorphosia and scotoma. This may help the patients seek medical care earlier.[28] The CNV associated with angioid streaks may respond favorably to anti-VEGF agents including ranibizumab, aflibercept, and bevacizumab.[29][30][31][29] The patients should wear protective glasses at work and sports glasses during sports to avoid trauma to the eyes as even trivial trauma can lead to multiple areas of subretinal hemorrhage. The subretinal hemorrhage can be subfoveal and may result in irreversible visual decline.[2]

Enhancing Healthcare Team Outcomes

The initial diagnosis and management of angioid streaks are primarily by the ophthalmologist, but the primary care provider and nurse practitioner usually do follow-up. Angioid streaks are generally asymptomatic and do not need any treatment. However, these eyes are more prone to develop subretinal hemorrhage after trivial trauma, and the clinical team and specialty-trained ophthalmic nurse should educate the patient on the use of protective eyewear. Due to the rarity of the use of medications, a pharmacist with a background in ophthalmic medications should assist the practitioner with the appropriate dosing of anti-VEGF agents.Screen all patients with angioid streaks for potential systemic associations. Examination of family members may give a clue to the systemic disease. Interprofessional collaboration is essential for systemic associations, including pseudoxanthoma elasticum and sickle cell disease. Collaborate with various specialties including, but not limited to, gastroenterology, cardiology, neurology, pulmonary medicine, and genetic specialists to manage pseudoxanthoma elasticum.


(Click Image to Enlarge)
<p>Fundus With Angioid Streaks. Color fundus photo of the right eye shows angioid streaks.</p>

Fundus With Angioid Streaks. Color fundus photo of the right eye shows angioid streaks.

Courtesy of Koushik Tripathy, MD

(Click Image to Enlarge)
<p>Angioid Streak, Glaucomatous Optic Nerve, and Choroidal Neovascularization</p>

Angioid Streak, Glaucomatous Optic Nerve, and Choroidal Neovascularization

Courtesy of Koushik Tripathy, MD

(Click Image to Enlarge)
<p>Angioid Streaks on Fundus

Angioid Streaks on Fundus. Angioid streaks and peau-d-orange appearance of the retina temporal to the fovea in a patient with pseudoxanthoma elasticum

Courtesy of Koushik Tripathy, MD



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