Angioid Streaks: A Comprehensive Guide to Differential Diagnosis and Management

Introduction

Angioid streaks are retinal findings characterized by crack-like disruptions in Bruch’s membrane, the supporting layer beneath the retina. These streaks are not blood vessels, as the name might suggest, but rather represent breaks in this vital membrane caused by mineralization and fragmentation of its elastic fibers. Angioid streaks significantly increase the risk of ocular complications, most notably choroidal neovascularization (CNV), where abnormal blood vessels grow beneath the retina. Bleeding and fluid leakage from these new vessels can lead to retinal damage, scarring, and potentially severe, irreversible central vision loss if the macula is affected. While treatments like anti-VEGF injections and photocoagulation can manage complications, early and accurate diagnosis is paramount.

A critical aspect of managing angioid streaks lies in differential diagnosis. Several other retinal conditions can mimic the appearance of angioid streaks, making accurate identification crucial for appropriate patient management and to rule out or identify associated systemic conditions. Angioid streaks can be idiopathic, occurring without a clear underlying cause, or they can be associated with various systemic diseases, including pseudoxanthoma elasticum (PXE), Paget’s disease of bone, sickle cell disease, and Ehlers-Danlos syndrome. Understanding the differential diagnosis is not only essential for ophthalmologists but also for any healthcare professional involved in the care of patients who may present with these retinal findings.

This article provides a comprehensive overview of angioid streaks, focusing on their differential diagnosis, underlying causes, clinical features, evaluation, and management strategies, equipping healthcare professionals with the knowledge to optimize patient care and minimize visual morbidity.

What are Angioid Streaks?

Angioid streaks are fundamentally disruptions within Bruch’s membrane, a thin, five-layered structure situated between the retinal pigment epithelium (RPE) and the choroid. This membrane plays a critical role in supporting the retina and facilitating nutrient exchange. In angioid streaks, Bruch’s membrane undergoes degeneration, calcification, and becomes brittle, leading to the characteristic crack-like appearance.

Pathophysiology: The exact mechanisms leading to Bruch’s membrane degeneration are not fully understood but are thought to involve a combination of factors, including:

Elastic Fiber Degeneration: Breakdown of elastic fibers within Bruch’s membrane is a key feature, often associated with systemic conditions like PXE.
Mineralization and Calcification: Deposition of calcium and other minerals makes the membrane less flexible and prone to fracturing.
Iron Deposition: Iron from hemolysis may contribute to membrane fragility, particularly in conditions like sickle cell disease.
Metabolic Disturbances: Impaired metabolism and abnormal deposition of glycosaminoglycans and glycoproteins can precede calcification.

Etiology: Angioid streaks can be classified as:

Idiopathic: Approximately half of all cases are idiopathic, meaning no underlying systemic condition is identified.
Secondary (Associated with Systemic Conditions): The most common systemic associations include:
- Pseudoxanthoma Elasticum (PXE) or Grönblad–Strandberg syndrome: The strongest association, with up to 87% of PXE patients developing angioid streaks. PXE is a genetic disorder affecting elastic tissue throughout the body.
- Paget Disease of Bone: A bone remodeling disorder affecting about 10% of Paget’s patients with angioid streaks.
- Hemoglobinopathies: Sickle cell disease is the most common, with 1-2% of patients developing angioid streaks. Other hemoglobinopathies are also linked.
- Ehlers-Danlos Syndrome: Historically associated, but recent literature suggests the association is less common than previously thought.
- Other less common associations: Marfan syndrome, acromegaly, hemochromatosis, diabetes, Sturge Weber syndrome, neurofibromatosis, trauma, and others.

Epidemiology:

Idiopathic angioid streaks typically appear in the sixth decade of life.
Patients with associated systemic conditions often present earlier.
PXE patients may present in their 30s, sickle cell disease patients in their 20s and 30s, and Paget’s disease patients later in life, around 67 years old.
No gender predilection is observed.
White individuals are more commonly affected than Black and Asian individuals.
Choroidal neovascularization is a major complication, causing central vision loss in a significant proportion (70-86%) of affected patients.

Differential Diagnosis of Angioid Streaks

Accurate differentiation of angioid streaks from other retinal conditions is crucial for proper diagnosis and management. The following conditions should be considered in the differential diagnosis:

Normal Retinal Vessels: Angioid streaks can sometimes be mistaken for retinal blood vessels during a cursory examination due to their linear appearance. However, key differentiating features include:
- Location: Angioid streaks are subretinal, lying beneath the retinal vessels.
- Appearance: Angioid streaks are typically jagged, irregular lines with serrated margins, while retinal vessels are smoother and more uniform. Angioid streaks also often have a variable caliber.
- Color: Angioid streaks can be gray, black, reddish, or pink, colors not typically associated with retinal vessels.
Myopic Lacquer Cracks: Lacquer cracks are also breaks in Bruch’s membrane, but they occur in highly myopic eyes due to stretching of the eyeball. Differentiating points:
- Context: Lacquer cracks are found in patients with high myopia, while angioid streaks may or may not be associated with myopia and are linked to systemic diseases.
- Appearance: Lacquer cracks are often finer, more spider-web like, and located in the posterior pole of highly myopic eyes. Angioid streaks are typically more prominent, broader, and radiate from the optic disc.
Reticular Dystrophy of the Retinal Pigment Epithelium (Reticular Pattern Dystrophy): This condition involves pigment changes in the RPE forming a “fishnet” pattern.
- Appearance: The pigment network in reticular dystrophy can sometimes form a circular pattern resembling the peripapillary ring of angioid streaks. However, reticular dystrophy lacks the distinct linear, crack-like appearance of angioid streaks. Fluorescein angiography can help differentiate, as reticular dystrophy shows characteristic hyperfluorescence.
Subretinal Tracks due to Ophthalmomyiasis Interna: These are tracks left by migrating parasite larvae beneath the retina.
- Appearance: Ophthalmomyiasis tracks are smooth, curvilinear, and can cross each other multiple times, unlike the jagged, non-crossing nature of angioid streaks. Patient history of potential exposure to flies and signs of inflammation may also be present in ophthalmomyiasis.
Subretinal Bands Associated with Retinal Detachment (Chronic or Surgically Repaired): Fibrous bands can form beneath the retina after retinal detachment.
- Context: A history of retinal detachment is key. These bands are typically broader and less defined than angioid streaks and are not radiating from the optic disc in the same characteristic manner.
Peripheral Punched-Out Scars (PPHS) / Presumed Ocular Histoplasmosis Syndrome: These are chorioretinal scars, often in the periphery.
- Location and Appearance: PPHS scars are typically peripheral, round or oval, and well-defined “punched-out” lesions. Angioid streaks are peripapillary and linear. PPHS lacks the characteristic streak appearance.
Choroidal Rupture: This is a break in the choroid, often due to trauma.
- Context: A history of ocular trauma is usually present. Initially, choroidal rupture presents with subretinal hemorrhage. After resolution, a scar may be visible, but it does not typically resemble the radiating pattern of angioid streaks.
Central Serous Retinopathy (CSR): CSR involves serous detachment of the neurosensory retina.
- Appearance: CSR presents as a localized retinal detachment, often with a characteristic fluid pattern on OCT. It lacks the linear streaks of angioid streaks. FA in CSR shows typical ink-blot or smokestack leakage patterns, different from angioid streak findings.
Choroidal Sclerosis: This refers to a diffuse sclerosis of the choroidal vessels.
- Appearance: Choroidal sclerosis causes more diffuse choroidal changes, often with a yellowish or pale fundus appearance. It does not present with the distinct, linear streaks of angioid streaks.
Exudative Age-Related Macular Degeneration (AMD): While choroidal neovascularization is a common complication in both angioid streaks and AMD, the underlying retinal findings differ.
- Differentiation: In AMD, drusen and other age-related macular changes are typically present. Angioid streaks themselves are distinct linear breaks, not drusen. The age of onset and associated systemic conditions also help differentiate.
Metastatic Choroidal Tumor: In rare cases, a metastatic tumor in the choroid could be considered in the differential diagnosis, especially if the findings are unilateral or atypical.
- Atypical Presentation: If the streaks are unilateral, rapidly progressing, or associated with other unusual features, metastatic tumor should be considered, particularly in patients with a history of systemic cancer. Imaging and systemic evaluation would be necessary.
Toxoplasmosis Retinochoroiditis: Scars from toxoplasmosis can sometimes be in the posterior pole.
- Appearance and History: Toxoplasmosis scars are typically chorioretinal scars, often with pigment clumping and atrophy. A history of congenital toxoplasmosis or active retinitis might be present. Toxoplasmosis scars lack the linear, radiating pattern of angioid streaks.

Understanding these differential diagnoses and carefully evaluating the clinical context, ophthalmoscopic appearance, and ancillary testing results are critical for accurately diagnosing angioid streaks and guiding appropriate management.

Clinical Features and Diagnosis

Angioid streaks are often bilateral and can be asymptomatic initially. Symptoms arise when the streaks involve the fovea or when choroidal neovascularization develops in the macular region.

Symptoms:

Metamorphopsia (distortion of straight lines): An early symptom of macular involvement.
Micropsia (objects appearing smaller than they are): Another symptom of macular involvement.
Decreased visual acuity: Occurs with foveal involvement or CNV.
Color vision loss: May occur as vision deteriorates.

Ophthalmoscopic Examination:

A comprehensive ocular examination is essential and should include:

Visual acuity testing
Refraction
Intraocular pressure measurement
Ocular motility assessment
Examination of ocular adnexa, lacrimal system, cornea, anterior chamber, iris, lens, and pupils (including assessment for relative afferent pupillary defect)
Detailed fundus examination

Clinical Characteristics of Angioid Streaks on Funduscopy:

Jagged, irregular lines with serrated margins: Radiating outwards from the optic disc.
Variable caliber: Similar in width to retinal vessels, ranging from 50 to 500 µm.
Subretinal location: Appear to be beneath the retinal vessels.
Interconnected streaks: Often forming a ring-like pattern around the optic disc.
Color: Gray, black, reddish, or pink.
Macular involvement: Streaks may extend into the macula.
Abrupt tapering: Streaks typically taper away from the optic disc.

Alt text: Fundus photograph of the right eye showing prominent angioid streaks radiating from the optic disc, characterized by jagged edges and varying widths.

Associated Features:

Peau d’orange appearance of the fundus: Speckled yellowish mottling, often temporal to the macula, resembling orange peel skin. Highly associated with PXE.
Optic disc drusen: Hyaline bodies in the optic nerve head, also more common in PXE.
Peripapillary chorioretinal degeneration, focal peripheral chorioretinal scars, and reticular pigment dystrophy of the macula.
Optic nerve atrophy: May be seen in Paget’s disease.
Macular thinning or pigmentary changes: Usually bilateral, without significant hemorrhage or exudates initially.
Crystalline bodies and comet-shaped lesions: Small, round, subretinal lesions, especially in PXE. Comet lesions are considered pathognomonic for PXE.
Subretinal or submacular hemorrhage: May occur spontaneously or after minor trauma.

Alt text: Fundus image revealing angioid streaks and a distinct peau d’orange appearance in the temporal macula, a hallmark finding in pseudoxanthoma elasticum.

Severe Visual Impairment is often due to:

Choroidal Neovascularization (CNV): The most serious complication, leading to serous and hemorrhagic detachment of the fovea.
Choroidal Rupture: Often from minor trauma, leading to submacular hemorrhage.
Foveal involvement by a streak: Direct damage to RPE and choriocapillaris.

Alt text: Color fundus photograph demonstrating choroidal neovascularization associated with angioid streaks and a glaucomatous optic disc, highlighting the severe complications possible with angioid streaks.

Diagnostic Investigations:

Fluorescein Angiography (FA): Helps visualize Bruch’s membrane cracks and detect CNV. Angioid streaks show hyperfluorescence in late phases due to staining. CNV shows leakage.
Indocyanine Green Angiography (ICGA): Superior to FA for detecting choroidal neovascularization and peau d’orange appearance.
Optical Coherence Tomography (OCT) and OCT Angiography (OCTA): OCT reveals retinal structural changes, edema, and CNV. OCTA non-invasively visualizes retinal and choroidal vasculature.
Ultrasound: Can detect optic nerve head drusen, especially in PXE.
Systemic Evaluation: Based on clinical suspicion, evaluate for associated systemic conditions (PXE, Paget’s, Sickle Cell) with appropriate blood tests, genetic testing, and imaging.

Management and Treatment

Asymptomatic Angioid Streaks:

Observation: Regular monitoring with ophthalmic examinations is usually sufficient.
Patient Education: Educate patients about the risk of complications and the importance of prompt reporting of new symptoms.
Protective Eyewear: Recommend protective eyewear to prevent choroidal rupture from minor trauma.

Choroidal Neovascularization (CNV) Secondary to Angioid Streaks:

Anti-VEGF Therapy: First-line treatment. Intravitreal injections of anti-VEGF agents (ranibizumab, aflibercept, bevacizumab, brolucizumab) can effectively regress CNV and improve or stabilize vision.
Laser Photocoagulation: Historically used, but outcomes are generally poor with high recurrence rates. Limited role in current practice.
Photodynamic Therapy (PDT): May be used in combination with anti-VEGF therapy in some cases, although anti-VEGF monotherapy is now preferred.
Surgical Options: Macular translocation surgery, autologous RPE/choroid transplantation, and surgical removal of CNV membranes are considered in rare, refractory cases despite anti-VEGF treatment.

Regular Follow-up:

Frequent ophthalmic examinations, including OCT and angiography as needed, are crucial to monitor for CNV development or recurrence and to assess treatment response.

Prognosis and Complications

Prognosis:

The visual prognosis for patients with angioid streaks, especially those developing CNV, is generally guarded.
CNV develops in a high percentage (72-86%) of patients over time.
Once CNV occurs in one eye, the other eye is at high risk within 18 months.
Visual loss from minor trauma is a significant risk.
Patients with PXE tend to have a poorer visual prognosis compared to those with sickle cell disease-associated angioid streaks. Sickle cell angioid streaks often have a more benign course, and CNV is less common.

Complications:

Subretinal Hemorrhage: Due to choroidal rupture after minor trauma.
Choroidal Neovascularization (CNV): The most vision-threatening complication.
Foveal Atrophy and Thinning: Direct damage to the macula.
Vision Loss: Can be significant and permanent, especially if CNV involves the fovea.

Patient Education and Deterrence

Early Detection: Emphasize the importance of regular comprehensive eye examinations, especially for individuals with known systemic associations like PXE, Paget’s, or sickle cell disease, and for family members of affected individuals.
Self-Monitoring: Teach patients to use the Amsler grid at home to monitor for metamorphopsia and scotoma, prompting them to seek prompt medical attention if changes occur.
Protective Eyewear: Stress the necessity of wearing protective eyewear, such as rigid goggles, during sports and activities with a risk of eye trauma, even minor blunt trauma.
Prompt Reporting of Symptoms: Instruct patients to immediately report any new symptoms like decreased vision, central vision disturbances, distorted vision, or depth perception problems.
Genetic Counseling: For patients with PXE or other inherited conditions, genetic counseling may be appropriate.

Enhancing Healthcare Team Outcomes

Managing patients with angioid streaks effectively necessitates a collaborative, interprofessional approach. Ophthalmologists are central to diagnosis and treatment, but primary care physicians, advanced practice clinicians, and other specialists are crucial for identifying and managing associated systemic conditions. Pharmacists ensure appropriate medication management, and nurses play a vital role in patient education and follow-up care. Effective communication and coordination within the healthcare team are essential to optimize patient outcomes, minimize vision loss, and provide holistic, patient-centered care.

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