Background

Angioid streaks, also known as Knapp’s striae, are a unique and visually significant ophthalmic manifestation that often captivates the attention of medical professionals and researchers alike. These intricate and delicate lines observed in the retina have long intrigued the field of ophthalmology due to their association with various systemic and ocular conditions.  

Initially described over a century ago, angioid streaks were first observed in association with pseudoxanthoma elasticum (PXE), a rare genetic disorder affecting various organs’ connective tissue. However, as research has progressed, it has become evident that these streaks can also be linked to other underlying conditions, such as Ehlers-Danlos syndrome, Paget’s disease of bone, and various systemic inflammatory disorders.

The complex interplay between genetic predisposition, connective tissue abnormalities, and vascular fragility has led researchers to unravel the mysteries surrounding angioid streaks and their implications for both ocular and systemic health. 

Epidemiology

Age: Angioid streaks can develop at any age, but they are most seen in individuals aged 40 to 60 years. 

Gender: There is no strong gender predilection for angioid streaks; they occur roughly equally in males and females. 

Ethnicity: There seems to be some variation in the prevalence of angioid streaks based on ethnic background. For instance, some studies have suggested a higher prevalence in individuals of European descent. 

Associated Conditions: Angioid streaks can be associated with certain systemic conditions, such as: 

Pseudoxanthoma elasticum (PXE): This hereditary disorder affects connective tissues and is the most common condition associated with angioid streaks. 

Ehlers-Danlos syndrome: Some subtypes of Ehlers-Danlos syndrome, a group of connective tissue disorders, can also be linked to angioid streaks. 

Paget’s disease of bone: Rarely, angioid streaks can occur in individuals with Paget’s disease, a bone disorder. 

Anatomy

Pathophysiology

Genetic Factors: In instances of pseudoxanthoma elasticum (PXE), an uncommon hereditary condition triggered by genetic mutations within the ABCC6 gene, there is a disturbance in the conveyance of specific molecules within the body. This disruption leads to the accumulation of calcium and other mineral deposits in various tissues, including the Bruch’s membrane of the eye. These deposits weaken the membrane, making it more susceptible to cracking. 

Abnormal Elastic Fibers: The accumulation of abnormal elastic fibers within the Bruch’s membrane, as seen in PXE, can contribute to its weakening. Elastic fibers normally provide structural support and flexibility to tissues, but when they become disorganized or calcified, they lose their function and integrity. 

Vascular Changes: The vascular changes in the choroid, which lies just beneath the Bruch’s membrane, can also play a role. These changes may involve alterations in blood flow and blood vessel integrity. Blood vessel abnormalities can lead to local hypoxia (low oxygen levels) and subsequent tissue damage, contributing to the development of cracks. 

Calcium and Mineral Deposition: In cases of PXE, the abnormal accumulation of calcium and minerals in the Bruch’s membrane weakens its structural integrity. These deposits can disrupt the normal architecture of the membrane and create areas of vulnerability that can lead to the formation of angioid streaks. 

Inflammation: Chronic inflammation within the eye can contribute to the breakdown of tissues, including the Bruch’s membrane. Inflammatory mediators can lead to tissue remodeling, collagen degradation, and weakening of the membrane, making it more susceptible to cracks. 

Mechanical Stress: Mechanical stress due to eye movement, changes in intraocular pressure, or trauma can exacerbate the vulnerability of the Bruch’s membrane. Weakened areas of the membrane are more likely to undergo microscopic fractures or cracks in response to these stresses. 

Etiology

Pseudoxanthoma Elasticum (PXE): PXE is a rare genetic disorder that affects the elastic fibers in various tissues, including the skin, blood vessels, and eyes. Mutations in the ABCC6 gene are commonly associated with PXE. In PXE, abnormal mineralization of tissues can weaken the Bruch’s membrane, making it more susceptible to cracks and breaks, which can lead to angioid streaks. 

Ehlers-Danlos Syndrome (EDS): EDS is a group of connective tissue disorders that can affect various parts of the body, including the eyes. Certain types of EDS can lead to weakening of the Bruch’s membrane and contribute to the development of angioid streaks. 

Pseudoxanthoma Elasticum-like Syndrome: This is a condition similar to PXE, but without mutations in the ABCC6 gene. It can also cause mineralization and weakening of tissues, including the Bruch’s membrane. 

Other Genetic Factors: While PXE and related conditions are known to be linked to angioid streaks, there may be other genetic factors that contribute to the development of these streaks. 

Systemic Diseases: Certain systemic diseases, such as Paget’s disease (a disorder of bone metabolism) and sickle cell disease (a hereditary blood disorder), have been associated with an increased risk of developing angioid streaks. 

Trauma: Physical trauma to the eye or head can potentially cause damage to the Bruch’s membrane and lead to the formation of angioid streaks. 

Calcification and Mineralization: The deposition of calcium and other minerals in the Bruch’s membrane has the potential to compromise its integrity, increasing its susceptibility to the formation of fractures. 

Genetics

Prognostic Factors

The untreated individuals diagnosed with choroidal neovascularization typically experience an unfavorable visual prognosis. While the majority of patients affected by pseudoxanthoma elasticum usually live a normal lifespan, premature mortality may arise from conditions such as cerebral hemorrhage,myocardial infarction and gastrointestinal hemorrhage. 

Clinical History

Angioid streaks are commonly linked with the adult population, particularly individuals in their middle-aged years or beyond. While these streaks are frequently observed in people aged 40 and above, they can also manifest in younger adults. Angioid streaks are a rare medical condition characterized by breaks or cracks in the Bruch’s membrane, a layer of tissue in the eye. They can be associated with certain systemic conditions, such as pseudoxanthoma elasticum (PXE), Paget’s disease of bone, and other connective tissue disorders. 

Physical Examination

Visual Acuity Test: This standard eye test assesses how well a person can see at various distances. It’s an initial step to identify any visual impairment or changes that might be linked to angioid streaks. 

Fundoscopy (Ophthalmoscopy): This is a key component of the examination. The ophthalmologist uses an ophthalmoscope to examine the inside of the eye, including the retina and choroid. Angioid streaks appear as thin, branching, irregular lines radiating outward from the optic nerve, and they may be associated with pigmentation changes. 

Fluorescein Angiography: This examination requires the introduction of a unique dye (fluorescein) into a vein, typically located in the arm. Subsequently, images are taken while the dye travels through the retinal blood vessels. Its purpose is to detect instances of leakage, neovascularization, and alterations in blood circulation that could potentially correlate with angioid streaks. 

Optical Coherence Tomography (OCT): OCT is a non-invasive imaging technique that provides detailed cross-sectional images of the retina and its layers. It’s particularly useful for identifying abnormalities beneath the surface of the retina, such as choroidal neovascular membranes, which can result from angioid streaks. 

Age group

Associated comorbidity

Associated Comorbidities: 

Pseudoxanthoma Elasticum (PXE): PXE is a hereditary disorder that affects the elastic tissues in various parts of the body, including the eyes. It often leads to the development of angioid streaks, which can cause vision loss. PXE is one of the most common underlying causes of angioid streaks. 

Ehlers-Danlos Syndrome (EDS): EDS is a group of genetic disorders that affect connective tissues. Some forms of EDS can lead to the development of angioid streaks due to the weakened connective tissues in the eye. 

Paget’s Disease of Bone: This disorder involves abnormal bone remodeling, which can affect the eye and lead to the formation of angioid streaks. 

Activities: 

Trauma: Damage to the eye, whether caused by trauma or injury, has the potential to result in the emergence of angioid streaks. The occurrence of these streaks can be influenced by incidents of blunt force trauma or injury affecting the vicinity of the eye. 

Physical Strain: Activities that involve excessive physical strain or pressure on the eyes, such as heavy lifting or activities that increase intraocular pressure, could potentially contribute to the development or progression of angioid streaks. 

Associated activity

Acuity of presentation

Choroidal Neovascularization (CNV): New blood vessels can grow through the cracks in the Bruch’s membrane, leading to bleeding and fluid leakage, which can impair central vision. This is the most common cause of vision loss associated with angioid streaks. 

Retinal Detachment: The cracks in the Bruch’s membrane might weaken the underlying structures, increasing the risk of retinal detachment, which can cause vision loss if not treated promptly. 

Macular Scarring: The bleeding and scarring caused by CNV can result in permanent damage to the macula, leading to central vision loss. 

Differential Diagnoses

Pseudoxanthoma Elasticum (PXE): PXE is a hereditary disorder that affects elastic tissue in the body, including the skin, eyes, and blood vessels. Like angioid streaks, PXE can cause breaks in Bruch’s membrane, leading to vision problems and other ocular manifestations. 

Retinal Detachment: Retinal detachment can lead to symptoms like those of angioid streaks, such as visual disturbances and scotomas (blind spots). It’s important to rule out retinal detachment as a cause of these symptoms. 

Macular Degeneration: Age-related macular degeneration (AMD) can also lead to changes in the retina that affect central vision. While the underlying mechanisms are different, the visual symptoms may overlap with those of angioid streaks. 

Retinal Pigment Epithelium Tears: Tears or disruptions in the retinal pigment epithelium (RPE) can resemble angioid streaks on clinical examination and imaging. 

Ocular Histoplasmosis Syndrome (OHS): OHS is an inflammatory condition that can lead to the formation of choroidal neovascularization and other retinal changes, which may mimic the appearance of angioid streaks. 

Myopic Degeneration: Severe myopia (nearsightedness) can result in various retinal changes, including breaks in Bruch’s membrane, which may appear like angioid streaks. 

Choroidal Ruptures: Traumatic choroidal ruptures can lead to disruptions in Bruch’s membrane, resembling angioid streaks. 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Observation and Lifestyle Modification: In some cases, especially when the angioid streaks are stable and not causing significant visual impairment, regular monitoring, and lifestyle adjustments (like avoiding high-impact activities that could worsen retinal damage) might be recommended. 

Management of Underlying Condition (PXE): Since angioid streaks are often associated with PXE, managing the underlying condition is crucial. This can involve a multidisciplinary approach, potentially involving dermatologists, ophthalmologists, and other specialists. Modifications in one’s way of life, such as refraining from smoking and safeguarding the skin against excessive sun exposure, could be advised. 

Intravitreal Injections: In some cases, intravitreal injections of medications like anti-vascular endothelial growth factor (anti-VEGF) drugs could be considered. These medications target abnormal blood vessel growth in the retina and might help in specific cases of retinal damage. 

Laser Therapy: Laser treatment, such as photodynamic therapy (PDT), might be used to target and seal abnormal blood vessels in the retina. This can help manage complications like choroidal neovascularization, which can lead to fluid leakage and further vision loss. 

Subretinal Surgery: In advanced cases with severe visual impairment due to complications like subretinal neovascularization, surgical interventions might be considered. These surgeries aim to remove or repair damaged areas of the retina. 

Low Vision Aids and Rehabilitation: For individuals with significant visual impairment that cannot be fully restored, low vision aids and visual rehabilitation programs can help maximize the use of their remaining vision. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-angioid-streaks

Regular Eye Examinations: Regular eye checkups conducted by an ophthalmologist are crucial for overseeing the advancement of angioid streaks and detecting any potential complications at an early stage. 

Blood Pressure Management: High blood pressure can exacerbate the effects of angioid streaks. It is essential to effectively manage blood pressure to avoid additional harm to the blood vessels within the eye. 

Smoking Cessation: Smoking is known to accelerate the progression of angioid streaks and increase the risk of associated complications. Ceasing smoking can contribute to a decrease in the likelihood of exacerbating symptoms. 

Protection from Trauma: Since trauma to the eye can worsen angioid streaks and cause bleeding, it’s important to take precautions to avoid injury to the eye. 

Effectiveness of photosensitizers in treating angioid streaks

Verteporfin (Visudyne) 

Verteporfin is injected intravenously into the patient’s bloodstream. 

A specific wavelength of light (usually in the red or near-infrared range) is then applied to the affected eye. This light activates the verteporfin that has accumulated in the abnormal blood vessels. 

Once activated, verteporfin generates reactive oxygen species (ROS), which can damage the abnormal blood vessels. This can help to close or damage these vessels, slowing down the growth and leakage of new blood vessels. 

Use of antineoplastic agents, monoclonal antibody in treating angioid Streaks

Ranibizumab (Lucentis) 

Ranibizumab, classified as a monoclonal antibody fragment, finds application in the treatment of diverse ocular conditions, mainly encompassing instances where there is anomalous growth of blood vessels within the retina. Its mechanism of action revolves around the specific targeting of vascular endothelial growth factor (VEGF), a pivotal protein accountable for stimulating the development of fresh vascular structures.

In conditions like AMD and diabetic retinopathy, increased VEGF levels contribute to abnormal blood vessel growth in the retina, leading to vision problems. By inhibiting VEGF, ranibizumab helps to reduce the growth of these abnormal blood vessels, which can improve or stabilize vision in affected individuals. 

Role of <a class="wpil_keyword_link" href="https://medtigo.com/drug/tetrahydrozoline-ophthalmic" title="ophthalmic" data-wpil-keyword-link="linked">ophthalmic</a>, VEGF Inhibitors in treating angioid streaks

Aflibercept intravitreal (Eylea) 

Aflibercept (brand name Eylea) is a medication that belongs to a class of drugs called anti-VEGF (vascular endothelial growth factor) agents. Its main application lies in addressing different ocular ailments characterized by irregular growth of blood vessels within the retina. These conditions encompass age-related macular degeneration (AMD), diabetic macular edema (DME), and macular edema resulting from retinal vein occlusion (RVO). 

Aflibercept works by binding to and inhibiting the activity of VEGF, a protein that promotes the growth of new blood vessels. In conditions like AMD, DME, and RVO, excess VEGF plays a role in the atypical development of blood vessels and their subsequent leakage, which has the potential to harm the retina and result in a decline in vision health. By blocking VEGF, aflibercept helps reduce the growth of these abnormal blood vessels and prevents fluid leakage, thus potentially improving vision and preventing further damage. 

Anti-VEGF Therapy: Anti-vascular endothelial growth factor (VEGF) medications, such as intravitreal injections of drugs like ranibizumab or aflibercept, may be used to manage complications like choroidal neovascularization (abnormal blood vessel growth under the retina). 

Laser Photocoagulation: Laser therapy may be employed to treat small choroidal neovascular membranes that develop because of angioid streaks. Laser photocoagulation can help seal off abnormal blood vessels and reduce the risk of bleeding. 

Subretinal Surgery: In cases of significant subretinal bleeding, surgical intervention may be required to remove the blood and prevent further damage to the retina. This procedure aims to improve visual outcomes and manage complications. 

Submacular surgery: The medical procedure of submacular surgery for angioid streaks encompasses the extraction of anomalous tissue situated beneath the macula, the central retinal area accountable for precise and intricate eyesight. Angioid streaks are a characteristic finding in certain medical conditions, such as pseudoxanthoma elasticum (PXE) and other inherited disorders, which can lead to breaks or cracks in the Bruch’s membrane—a layer of tissue that supports the retina’s blood vessels. 

Diagnosis and Assessment: The first step is to diagnose angioid streaks through a comprehensive eye examination, including a dilated fundus examination and retinal imaging techniques. It’s important to assess the extent and severity of the streaks and any associated complications like CNV or hemorrhages. 

Underlying Cause Management: If angioid streaks are associated with an underlying systemic condition, such as PXE, managing the primary condition is crucial. In the case of PXE, managing cardiovascular risk factors and optimizing overall health can help slow down the progression of both the systemic condition and the ocular manifestations. 

Risk Factor Management: Patients with angioid streaks, especially those with CNV or hemorrhages, need to manage risk factors that can exacerbate the condition. These include avoiding trauma to the eye, managing hypertension, and avoiding blood thinning medications if possible. 

Anti-VEGF Therapy: Choroidal neovascularization (CNV) is a common complication of angioid streaks that can lead to vision loss. Anti-vascular endothelial growth factor (anti-VEGF) therapies, such as injections of drugs like ranibizumab or aflibercept, are often used to treat CNV and prevent its recurrence. 

Medication

Future Trends

Media Gallary

References

Angioid Streaks – StatPearls – NCBI Bookshelf (nih.gov) 

Angioid Streaks – PubMed (nih.gov)