Angioid Streaks 

Updated: Jul 23, 2021
Author: Mohammad Abusamak, MD, FICO, FRCS(Glasg), MRCS(Edin); Chief Editor: Andrew G Lee, MD 

Overview

Background

In 1889, Doyne first described angioid streaks in a patient with retinal hemorrhages secondary to trauma.[1] Angioid streaks, also known as Knapp striae, are irregular jagged dehiscences in the mineralized, degenerated, brittle Bruch membrane that typically form alongside force lines exerted by intrinsic and extrinsic ocular muscles that radiate in a centrifugal pattern emanating from the optic disc.[2] Knapp named them angioid streaks because of their resemblance to blood vessels.[2]  

Progression of angioid streaks. Large subretinal h Progression of angioid streaks. Large subretinal hemorrhage.
Same eye as in previous image, 11 months later. Pa Same eye as in previous image, 11 months later. Partial resolution of subretinal blood. Notice the old subretinal hemorrhage under the fovea and color change to white-yellow.
Late complication of choroidal neovascularization Late complication of choroidal neovascularization in angioid streaks. Same eye as in previous images, 5 years later. Notice the extensive scarring and subretinal exudates and dehemoglobinized blood.

Pathophysiology

Controversy about the pathophysiology of angioid streaks exists. In some diseases, including pseudoxanthoma elasticum (PXE) and Paget disease, the Bruch membrane may become calcified and brittle with subsequent development of cracks. However, cytoimmunochemistry and x-ray analysis had shown that the earliest abnormality in PXE was abnormal accumulation and metabolism of polyanions (ie, glycosaminoglycans, glycoproteins) within the Bruch membrane.

The lines of force within the eye resulting from the pull of intrinsic and extrinsic ocular muscles on the relatively fixed site of the optic nerve have been studied. Those lines of forces had the same configuration as the peripapillary interlacement and radial extensions of angioid streaks. Such forces acting on the Bruch membrane undoubtedly account for the configuration of the breaks. However, in sickle cell disease, Bruch membrane calcification is not a common part of the pathology.

It is believed that the pathology may be a combination of diffuse elastic degeneration of the Bruch membrane, iron deposition in elastic fibers from hemolysis with secondary mineralization, and impairment of nutrition because of sickling, stasis, and small vessel occlusion. Klien proposed a dual mechanism as a cause of these cracks in general, as follows: a primary abnormality of fibers of the Bruch membrane, and an increase in availability of metal salts or a tendency for their deposition, resulting in a secondary brittleness of the membranes.[3]

Epidemiology

Frequency

United States

Not known

International

Not known

Mortality/Morbidity

Moderate-to-severe central visual loss is mainly related to foveal involvement with a dehiscence of the underlying Bruch membrane or a neovascular membrane formation under the retina. Choroidal neovascularization (CNV) is the major cause of vision loss and affects 70-86% of patients with angioid streaks.

Race

White people are affected most. Two studies showed similar results: of all patients with angioid streaks, 66.2% of patients were white, compared with 29% of Asian origin and 3.7% of black people.[4, 5]

Sex

No sexual predilection exists.

Age

The age of onset is variable with the underlying etiology. In one study, the age of onset of 50 patients with angioid streaks was reported as follows:

  • Patients with PXE present in the third decade with a mean age of 51.7 years.

  • Patients with sickle cell disease tend to be in their second and third decades with a mean age of 41.7 years.

  • Patients with Paget disease tend to be older at the time of diagnosis with a mean age of 67 years.

  • Angioid streaks in patients with no systemic disease or with rare etiologies tend to present late in life with a mean age of 65.7 years. Rare etiologies include patients with peptic ulcer, diabetes, hypertension, arthritis, breast cancer, metastatic cancer, rheumatoid spondylitis, and heart disease.

Prognosis

A high risk of serious complications, such subretinal hemorrhage and serous detachment, exists. Bilateral involvement is the rule, although it may not be symmetrical. Among individuals in whom CNV begins to develop, 50% will develop CNV in the fellow eye within 18 months.[5, 6, 7] Families with affected individuals need screening and regular eye examinations for early detection of any progression.

Patient Education

Patients should be instructed to return if visual acuity decreases. Signs of decreased central visual acuity may include central blurred vision, difficulty in depth perception, and distortion of lines and objects.

Families and patients will benefit from using an Amsler grid to detect early changes in asymptomatic but high-risk individuals.

More emphasis should be placed on safety measures to avoid trauma even if trivial. Protective goggles are useful for young patients who participate in sports.

 

Presentation

History

Visual acuity is normal unless a leakage, bleeding, or Bruch membrane dehiscence involves the central macula. Distorted central vision (metamorphopsia) and micropsia can be early signs of macular involvement.

Physical

Ophthalmoscopic findings

At times, angioid streaks can be difficult to identify unless a careful examination of the posterior pole is performed.

Angioid streaks usually present as linear gray or dark red lines with irregular serrated edges lying beneath normal retinal blood vessels. The streaks intercommunicate in a ringlike fashion around the optic disc in 27% of cases and radiate outward in a tapering fashion from the peripapillary area in 73% of patients. The streaks run a convoluted course and tend to terminate abruptly. Angioid streaks usually do not extend past the equator. Associated findings in patients with angioid streaks are as follows:

  • Peau d'orange or leopard skin spotting, consisting of speckled yellowish mottling of the posterior pole mostly apparent in the temporal macula. This finding may antedate the appearance of angioid streaks. It is seen more frequently in patients with PXE and is caused by alterations at the level of the Bruch membrane as demonstrated by the diffuse pattern of hyperfluorescence on indocyanine green angiography (ICGA). Confluent areas of opacification visualized on imaging represent calcium deposition within the Bruch membrane, termed coquille d’oeuf (egg shell). It is hypothesized that calcium deposition weakens the Bruch membrane and subsequently leads to fractures, producing a cracked–egg-shell appearance. [8]
  • Peripapillary chorioretinal atrophy, focal peripheral chorioretinal scars (salmon spots), and reticular pigment dystrophy of the macula may be present at the time of diagnosis.
  • Optic nerve head drusen (hyaline bodies) may antedate the appearance of angioid streaks, and they may be the earliest clinical manifestations of PXE. As many as 25% of patients with angioid streaks have clinical or echographic evidence of disk drusen. These hyaline bodies were associated with neovascularization in the peripapillary area, and, in some patients, they were associated with acute visual loss due to the pressure effect on the optic nerve head.
  • Crystalline bodies typically are seen in the midperipheral fundus or inferior to the optic nerve. They are multiple, round, small, and subretinal lesions. Usually, these crystalline bodies cause some atrophy of the retinal pigment epithelium (RPE). In older patients, peripheral retinal scars and calcifications can be seen. [9]
  • Optic atrophy may be seen in patients with Paget disease of the bone. It cannot be explained solely on the basis of bony compression.
  • Papillophlebitis has been reported as an incidental finding in a female patient with angioid streaks who received a progestin implant. [10]

Severe visual impairment is caused by one of the following conditions in 70% of cases:

  • CNV with subsequent serous and hemorrhagic detachment of the fovea (most serious complication)
  • CNV development occurs in 72-86% of all patients over time. [11] Once a patient develops CNV in one eye, it becomes bilateral in 50% within 18 months of the initial diagnosis. [12]
  • Choroidal rupture secondary to trivial trauma with secondary hemorrhage involving the fovea
  • Foveal involvement by a streak with damage to RPE and choriocapillaris (may result in permanent loss of central visual acuity)

Causes

Idiopathic

In 50% of patients with angioid streaks, no associated systemic disease is present.

Systemic association

PXE is an uncommon inherited disorder of connective tissue. It has generalized effects on the elastin fibrils in the dermis, arterial walls, heart, gastrointestinal (GI) tract, and Bruch membrane, resulting in mineralization and deposition of phosphorus. The 4 types of inheritance of PXE include 2 of which are autosomal dominant and 2 of which are autosomal recessive. It is the most common systemic disorder associated with angioid streaks. Diagnosing PXE is important because 85% of patients develop ocular involvement, usually after the second decade of life. The combination of PXE and ocular involvement is referred to as Grönblad-Strandberg syndrome.

Histologically, degenerative changes and calcifications of the elastic tissues in the skin and arteries are present. The following systemic findings may help the ophthalmologist to confirm the diagnosis of angioid streaks secondary to PXE, as well as to take care of complications.

Dermatologic findings include yellow papules, "chicken skin" arranged in a linear or reticulate pattern, in plaques, over the side of the neck, antecubital fossae, axillae, groin, and paraumbilical area.

Cardiovascular manifestations include accelerated hypertension at an earlier age due to atherosclerosis, which may be related to renovascular disease, premature coronary artery disease, peripheral vascular disease, and mitral incompetence.

Some patients develop genitourinary bleeding as part of PXE.

Neurologic findings may include cerebrovascular accidents, intracranial aneurysms, and cerebral ischemia.

Paget disease

Paget disease is a chronic, progressive, and in some cases inherited disease, characterized by bone deformity. It may be confined to a few bones, or in some patients, it represents a generalized abnormality that gives rise to enlargement of the skull, kyphoscoliosis, deafness, and deformities of long bones. However, angioid streaks occur in fewer than 2% of patients. Osteoclastic activity with an osteoblastic reaction occurs. Although the etiology is unknown, some clinicians believe it is related to a slow virus infection, measles, or respiratory syncytial virus. Both males and females are affected equally.

Ehlers-Danlos syndrome

Ehlers-Danlos syndrome is a rare autosomal dominant disorder of collagen resulting from a deficiency of hydroxylysine. Ocular findings include epicanthal folds, keratoconus, high myopia, retinal detachment, blue sclera, ectopia lentis, and angioid streaks. Systemic associations include the following:

  • Skin and musculoskeletal - Thin hyperplastic skin that heals poorly, hyperextensible joints that may predispose to recurrent falls, hydrarthrosis, and pseudotumor formation over elbows and knees

  • Cardiovascular disease consists of bleeding diathesis, dissecting aneurysms, spontaneous rupture of large blood vessels, and mitral prolapse.

  • Others - Diaphragmatic hernias and diverticulum of the GI and respiratory tracts

Hemoglobinopathies

Hemoglobinopathies that are occasionally associated with angioid streaks include the following:

  • Homozygous sickle cell disease (Hb-SS)

  • Sickle cell trait (Hb-AS)

  • Sickle cell thalassemia (Hb-thal)

  • Sickle cell hemoglobin (Hb-SC)

  • Hemoglobin H (Hb-H)

  • Homozygous B-thalassemia major

  • Intermedia

  • Minor and hereditary spherocytosis

Advancing age and ethnicity

The frequency of angioid streaks increases with age; it is about 1.5% in younger patients and increases to 22% in older patients. Complications, such as macular degeneration and choroidal neovascular membranes, are uncommon in this subgroup of patients with angioid streaks. In general, choroidal neovascular membranes (CNVM) and serous detachments of the macula are less common in black patients.

Other systemic diseases

Other systemic diseases associated with angioid streaks include the following:

  • Aagenaes syndrome (lymphedema cholestasis syndrome 1) [13]
  • Abetalipoproteinemia
  • Acromegaly
  • Dwarfism
  • Diabetes mellitus
  • Hemochromatosis
  • Facial angiomatosis
  • Idiopathic thrombocytic purpura
  • Chronic familial hyperphosphatemia
  • Hypercalcinosis
  • Hyperphosphatemia [6]
  • Diffuse lipomatosis
  • Acquired hemolytic anemia
  • Myopia
  • Neurofibromatosis
  • Epilepsy
  • Senile elastosis
  • Sturge-Weber syndrome
  • Trauma
  • Tuberous sclerosis

 

 

Complications

Subretinal hemorrhage and serous detachment are common complications of angioid streaks. Incidence of subretinal hemorrhage and serous detachment caused by choroidal neovascularization is high, about 85% of all patients with PXE and 10-15% of patients with Paget disease of the bone. The disease is bilateral in all patients with an average age of onset older than 25 years. The greater the length and width of the angioid streaks, the greater the risk of CVN. The risk is even higher if the streaks are within 1 disc diameter of the foveola.[5, 6, 7] Ungureanu et al reported a case of neovascular glaucoma secondary to angioid streaks.[14]

 

DDx

Differential Diagnoses

 

Workup

Laboratory Studies

Only one half of patients with angioid streaks have a systemic association. General workup is important to diagnose and treat other aspects of the disease that may be life threatening, such as GI hemorrhage, heart disease, anemia, and pathological fractures.

Biochemical survey: Serum calcium, phosphorous, and alkaline phosphatase levels may be abnormal in untreated cases of Paget disease. Urinary excretion of pyridinoline crosslinks is a more specific and sensitive marker. In untreated patients, a close correlation between serum activity of alkaline phosphatase and urinary excretion of hydroxyproline exists. However, 10% of patients with Paget disease who are symptomatic have serum levels of alkaline phosphatase within the reference range.

Imaging Studies

Fluorescein angiography

Red-free photographs show radiating irregular curvilinear lines of variable width and configurations.

Red-free photograph of the optic nerve and posteri Red-free photograph of the optic nerve and posterior pole showing the cracks in the Bruch membrane. Notice the retinal arteries and veins crossing over the dark red streaks.

Early fluorescein angiography (FA) reveals either hyperfluorescence due to window transmission defects of atrophic RPE or uncommonly hypofluorescence due to atrophy or separation of underlying choriocapillaries, which results in nonfilling window defects.

Early fluorescein angiography showing the early hy Early fluorescein angiography showing the early hyperfluorescence, window defect, of the angioid streaks.

In late FA, some leakage at the margins of the streaks occurs from adjacent healthy choriocapillaries and from late staining of the sclera and deep choroidal vessels. The classic appearance of CNVM, RPE detachments, and serous or hemorrhagic detachments also may be noted on FA.

Late fluorescein angiography of the same eye as in Late fluorescein angiography of the same eye as in Media file 2. Notice the staining of the edges of the streaks. Also, staining in the center of the macula is present due to extension of the Bruch membrane crack. When compared to early fluorescein angiography, no active leakage is present.

Indocyanine green angiography

ICGA is superior to FA in defining occult choroidal neovascularizations. It shows angioid streaks in all eyes studies. Hyperfluorescent lines are visible in most cases. However, some patients exhibit hypofluorescence and tracklike fluorescence.

Peau d'orange appearance of the temporal macula can be seen on ICGA as a speckled pattern in the midperiphery. Hyperfluorescent lines look larger and more numerous than those seen on FA or red-free photographs.

Radiology studies

Radiographs of the head, abdomen, and lower extremities are helpful to show bone involvement in Paget disease of the bone and premature calcification of arteries in PXE.

Optical coherence tomography angiography

Optical coherence tomography angiography (OCTA) is a new noninvasive technique that constructs a three-dimensional image, providing information on both retinal structure and vascular flow.[15] It is superior to FA in terms of visualizing the intraretinal structures and requires no dye injection. A case report by Gal-Or et al used OCTA to identify CNV in a patient with angioid streaks. On OCTA, the CNV followed the path of the angioid streak, demonstrating breaks along the Bruch membrane.[16] This new imaging modality shows promise in monitoring CNV and in serving as a tool for early detection of CVN in patients with angioid streaks.[15, 16]

Other Tests

Retinal function tests

Visual acuity is normal, as long as no damage to the foveal RPE and no leakage from the choroid through the Bruch membrane and RPE occur.

Visual fields are normal unless the central macula is affected by the angioid cracks and RPE detachments.

Color vision is affected only when vision loss occurs and is similar to color vision in acquired macular diseases.

Electroretinography (ERG) findings are normal.

Electro-oculography (EOG) findings are normal in most cases. Findings may be subnormal in advanced cases.

Dark adaptation is normal.

GI studies

GI hemorrhage is common in patients with PXE.

Procedures

Dermatologic: Skin biopsy may provide important diagnostic clues in cases of PXE with angioid streaks.

 

Treatment

Medical Care

Initially, patients are asymptomatic and no indication for prophylactic treatment is present. Angioid streaks are a generalized disorder of the Bruch membrane.

Angioid streaks are an uncommon entity to be studied and are treated as part of a controlled and randomized study. Treatment methods are based mainly on individual experience and extrapolation from the Macular Photocoagulation Study Group. Patients with angioid streaks are at higher risk of choroidal rupture and subretinal hemorrhage secondary to mild blunt trauma.[17] They are advised to wear protective goggles and sports glasses when playing sports and during work.

Treatment options include observation, laser photocoagulation, and surgical removal of CNVM under the fovea. The Food and Drug Administration (FDA) approved the use of photodynamic therapy (PDT) for CNVM secondary to age-related macular degeneration (ARMD).

Observation

Initially, symptomatic patients complained of a decrease in their central visual acuity, and some developed distortion and metamorphopsia that was more disturbing than the associated central scotomas. Usually, central scotomas tend to increase in size if left untreated before subsequent scarring of the macula occurs.

Early at the time of diagnosis, more than 50% of patients had vision of 20/40 or better; one half of them became legally blind at an average follow-up period of 3.5 years. Most eyes had vision 20/200 or worse after age 50 years.

In one study, 11 untreated eyes with subretinal neovascular membranes all had a final visual acuity of counting fingers. Clarkson and Altman reported 29 patients seen on 2 occasions over a period of at least 6 months.[18] Decreased vision of 2 lines or greater on the Snellen chart occurred in 13 of 29 patients.[18]

Prophylactic laser treatment in clinically asymptomatic eyes without active choroidal neovascularization is not recommended. In one study, prophylactic treatment was associated with an increased incidence of neovascularization at the site of treatment. However, patients who received laser photocoagulation noticed a decrease in the size of their central scotomas and early relief from visual distortion.

Laser photocoagulation

Photocoagulation, including light (xenon) and argon, has been used since the early 1970s, although angioid streaks themselves were treated to stop their progression toward the macula. Early treatment experiences with light and laser photocoagulation were disappointing and discouraging. Some investigators discouraged laser treatment of CNVM in angioid streaks.

Some success with argon laser for lesions that are located at least 100 µm from the center of the foveal avascular zone (FAZ) has been reported.

Laser therapy is believed to slow the progression of the CNV toward the fovea and stabilizes vision. Moreover, it improves the quality of vision (ie, size of central scotoma, decreases metamorphopsia). Successful treatment of CNV may not improve central vision in some patients since dehiscences in the Bruch membranes may involve and damage the foveal RPE.

Many investigators found that laser treatment, if administered early and adequately to CNV lesions, may have a favorable result on long-term visual outcome.

Many patients needed multiple treatments because of persistent leakage and recurrence that occurred during the first 3 months.

Patients need to be monitored closely with Amsler grids and FA.

In several series, the recurrence rate was reported as high as 77% of patients who underwent laser treatment. Most recurrent CNVMs were subfoveal. The incidence of recurrence was higher in angioid streaks than in other conditions, such as ARMD, degenerative myopia, and histoplasmosis.

Treating CNVM associated with angioid streaks is sometimes challenging. Both occult and classic CNV can occur in the same eye and usually are located very close to the foveal avascular zone. RPE reaction is minimal around CNVM. Some of these membranes grow fast once they break through the Bruch membrane. Careful setup of laser power and spot size is important to prevent further damage to the brittle and mineralized Bruch membrane.

Transpupillary thermotherapy

Transpupillary thermotherapy (TTT) has been used in the treatment of macular CNV. The diode laser used in transpupillary thermotherapy results in less absorption of the RPE and allows for deeper penetration into the choriocapillaris.[6] Transpupillary thermotherapy has been reported in the literature as a treatment modality for CNV due to angioid streaks but has been unsuccessful.[6, 19] Ozdek et al reported an initial decrease in the size of the angioid streak, but it began to increase again at 3 months. The patient’s visual acuity remained stable; however, the CNV activity was not effectively decreased, leading to more retreatments.[19] Thus, transpupillary thermotherapy is not as effective as other treatment modalities in CNV due to angioid streaks and may lead to more unfavorable outcomes.[6, 19]

Photodynamic therapy

PDT is a modality approved by the FDA for the treatment of CNV secondary to ARMD. It uses a light activated drug (eg, verteporfin [Visudyne]) and applying a nonthermal red light in the range of 689 nanometers. The total energy delivered is 50 J/cm2 over a period of 83 seconds. The power of laser output can be adjusted according to size of CNV and ophthalmic lens magnification.

A study evaluated the short-term safety and visual effects after administering PDT in 13 patients with classic subfoveal CNV secondary to pathological myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. Most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1-week posttreatment, with complete absence of leakage in almost one half of the patients. Up to 4 treatments were found to have short-term safety even with re-treatment intervals as short as 4 weeks.

Karacorlu et al evaluated the safety and efficacy of PDT with verteporfin for subfoveal CNV associated with angioid streaks in 8 eyes and showed that PDT generally achieved a short-term cessation of or a decrease of fluorescein leakage from subfoveal CNVM without loss of vision in patients with angioid steaks.[20]

Long-term effects of PDT, especially in patients who may need multiple treatments, are unknown. Patients with angioid streaks are at higher risk of recurrent CNV.

Right eye, midphase arteriovenous, showing chorioc Right eye, midphase arteriovenous, showing choriocapillaris atrophic changes. This 45-year-old patient underwent 3 injections of Avastin and one session of half-time photodynamic therapy.
Same patient as in previous image, a few months be Same patient as in previous image, a few months before the Avastin injection and half-time photodynamic therapy.

Antiangiogenic agents

Recently, with the advent of antivascular endothelial antibodies, namely bevacizumab, ranibizumab, and aflibercept,[21, 22, 6] the treatment of choroidal neovascularization secondary to angioid streak has taken a great positive turn. Many patients are treated with anti–vascular endothelial growth factor (VEGF) therapy worldwide. The visual function showed stabilization over extended periods. Unfortunately, the recurrence rate is high and many patients need repeated injections to control the disease.[23, 24, 25, 26]

Bevacizumab

Teixeira et al, who first described the use of bevacizumab for CNV secondary to angioid streaks, reported an improvement in visual acuity and stabilization of disease.[27] Successful treatment with bevacizumab has been reported by several authors since.[27, 6, 28]

Ranibizumab

Tilleul et al showed visual improvement in 22 of 35 eyes (62.9%) after intravitreal injections of ranibizumab, along with a decrease in macular thickness in 45.7% of patients, and 77.1% showed no leakage at 4-year follow-up.[29, 30, 28] Ebran et al demonstrated improvement of visual acuity in 88.6% of 98 eyes following intravitreal ranibizumab injections. At 2-year follow-up, visual acuity remained stable, with a significant reduction in recurrence.[31] Finger et al showed that patients with early disease showed significant improvement in visual outcome compared to those with advance disease.[32, 28]

Aflibercept 

Intravitreal aflibercept has been described in case reports as treatment for refractory CNV secondary to angioid streaks. It has also been reported as the initial treating agent of CVN, with success.[21, 22] Makri et al reported on a 42-year-old white woman who presented with persistent CNVM and subretinal fluid that was treated with ranibizumab with no anatomical or functional improvement. After 3 loading doses of aflibercept, the patient showed increased vision and resolution of subretinal fluid.[33]

Combination low-fluence photodynamic therapy and ranibizumab

Combination low-fluence photodynamic therapy and ranibizumab were used successfully to treat cases of angioid streaks in many centers around the world.[34, 35]

Surgical Care

Submacular surgery

Patients with classic subfoveal CNVM are not candidates for laser photocoagulation therapy. In the past, they were left without treatment. However, advances in instrumentation and vitreoretinal surgical techniques have made it possible to remove CNVM without significant damage to RPE and neurosensory retina.

Eckstein et al reported encouraging short-term visual results in 31 consecutive patients with non–age-related subfoveal CNVM, including angioid streaks.[36] Visual acuity improved or remained the same in 25 of 31 eyes. Moreover, visual acuity improved by more than 2 lines in 5 eyes (16%). Older patients and those with atrophic RPE had the worst outcome. Recurrent CNV occurred in 11 eyes (35%). The presence of subfoveal blood was associated with a higher recurrence rate of membranes. There was no significant association between the final visual acuity and length of symptoms prior to surgery or preoperative vision.[36]

Transplantation of autologous full-thickness RPE and choroidal patch

Parolini et al described a case of a 53 year-old man with subfoveal CNV secondary to angioid streaks who underwent transplantation of an autologous full-thickness RPE and choroidal patch. The patient experienced significant visual improvement, from 20/200 to 20/40 and J2, at nearly 6 months posttreatment. At 2.5 years, there was no recurrence of CVN, and the patient’s vision remained stable.[37]

Activity

Patients with angioid streaks have a high risk of choroidal rupture and subretinal hemorrhage secondary to mild blunt trauma. It is recommended that patients wear protective sports glasses whenever applicable.

Long-Term Monitoring

Screening and follow-up examination by means of Amsler grid and ophthalmoscopic examination, including FA, may be necessary to detect CNVM and to treat recurrences.

Patients who undergo laser treatment or surgery need close follow-up care during the first 3 months of treatment. If they stay asymptomatic and no FA leakage occurs, follow-up care every 6 months is recommended.

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Photosensitizers

Class Summary

Effects can induce vascular occlusion.

Verteporfin (Visudyne)

A benzoporphyrin derivative monoacid (BPD-MA), consists of equally active isomers BPD-MAC and BPD-MAD, which can be activated by low-intensity, nonthermal light of 689-nm wavelength. After activation with light and in presence of oxygen, verteporfin forms cytotoxic oxygen free radicals and singlet oxygen. Singlet oxygen causes damage to biological structures within range of diffusion. This leads to local vascular occlusion, cell damage and cell death. In plasma, verteporfin is transported primarily by low-density lipoproteins (LDL). Tumor and neovascular endothelial cells have increased specificity and uptake of verteporfin because of their high expression of LDL receptors. Effect can be enhanced by use of liposomal formulation.

Antineoplastic Agent, Monoclonal Antibody

Class Summary

Antivascular growth factor inhibitor stops new blood vessel formation.

Ranibizumab (Lucentis)

Recombinant humanized IgG1-kappa isotype monoclonal antibody fragment designed for intraocular use. Indicated for neovascular (wet) age-related macular degeneration (ARMD). In clinical trials, about one third of patients had improved vision at 12 mo that was maintained by monthly injections. Binds to VEGF-A, including biologically active, cleaved form (ie, (VEGF110). VEGF-A has been shown to cause neovascularization and leakage in ocular angiogenesis models and is thought to contribute to ARMD disease progression. Binding VEGF-A prevents interaction with its receptors (ie, VEGFR1, VEGFR2) on surface of endothelial cells, thereby reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation.

Ophthalmics, VEGF Inhibitors

Aflibercept intravitreal (Eylea)

EYLEA (aflibercept) is a recombinant fusion protein consisting of portions of human vascular endothelial growth factor (VEGF) receptors 1 and 2 extracellular domains fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is a dimeric glycoprotein with a protein molecular weight of 97 kilodaltons (kDa) and contains glycosylation, constituting an additional 15% of the total molecular mass, resulting in a total molecular weight of 115 kDa. Aflibercept is produced in recombinant Chinese hamster ovary (CHO) cells.

Afliberceptis a sterile, clear, and colorless to pale yellow solution. EYLEA is supplied as a preservative-free, sterile, aqueous solution in a single-use, glass vial designed to deliver 0.05 mL (50 microliters) of aflibercept (40 mg/mL in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 20, and 5% sucrose, pH 6.2).