S E CT I O N
7Hematologic and Cardiovascular Disorders
80 CAROTID CAVERNOUS FISTULA
853.0
(Dural Shunt Syndrome, Carotid Artery-
Cavernous Sinus Fistula, Arteriovenous Communication or Arteriovenous Fistula)
M. Tariq Bhatti, MD
Durham, North Carolina
Keith Robertson Peters, MD, ABR, CAQ VIR, CAQ NR
Gainesville, Florida
INTRODUCTION
Carotid cavernous fistulas represent an abnormal arteriovenous communication between the cavernous sinus (a venous structure) and the carotid arterial system (internal and/or external carotid arteries). Carotid cavernous fistulas can be classified as: high flow vs. low flow, direct vs. indirect (dural) or traumatic vs. spontaneous. The Barrow classification categorizes the fistulas depending on the angiographic pattern of the arterial flow. Depending on the type of carotid cavernous fistula and the pattern of venous drainage (anterior or posterior) the clinical manifestations can be variable and diverse.
ETIOLOGY/INCIDENCE
Most carotid cavernous fistulas are of the direct type and caused by head trauma (70%–90%). Dural carotid cavernous fistulas are thought to be congenital in etiology and are more commonly seen in middle-aged or elderly women often associated with systemic arterial hypertension, atherosclerotic vascular disease and connective tissue disorders.
COURSE/PROGNOSIS
Direct carotid cavernous fistulas can be life threatening due to severe epistaxis or intracranial (intracerebral or subarachnoid) hemorrhage therefore nearly all require intervention. In comparison, if left untreated dural carotid cavernous fistulas rarely result in neurological sequela but can be associated with significant ocular morbidity. Up to 50% of dural carotid cavernous fistula will close without treatment. Acute worsening of the ocular manifestations may occur from increased blood flow
through the fistula or spontaneous thrombosis of the superior ophthalmic vein.
DIAGNOSIS
Clinical signs and symptoms
(Figure 80.1)
●Red eye due to episcleral venous congestion (corkscrew episcleral vessels).
●Conjunctival chemosis.
●Eyelid or facial edema.
●Elevated intraocular pressure (asymmetric ocular pulse).
●Pulsating exophthalmos.
●Diplopia due to ocular motor cranial neuropathy or extraocular muscle congestion.
●Orbital (ocular) pain or headache.
●Orbital bruit (approximately 50% of dural fistulas).
●Retinal vascular congestion and hemorrhages.
●Visual loss due severe corneal exposure, glaucoma, retinopathy or optic neuropathy.
Laboratory findings
●Orbital ultrasonography: dilated superior ophthalmic vein and enlarged extraocular muscles.
●Computed tomography: dilated superior ophthalmic veins, dilated cerebral veins, and enlarged extraocular muscles.
●Magnetic resonance imaging: abnormal flow voids, dilated superior ophthalmic vein, enlarged extraocular muscles, and orbital congestion.
●Magnetic resonance angiography (maximum intensity projection and source images): flow signal abnormalities.
●Six-vessel cranial digital subtraction angiography (diagnostic procedure of choice): characterization of the arterial supply and venous drainage of fistula.
Differential diagnosis
●Chronic conjunctivitis.
●Orbital cellulites.
●Thyroid eye disease.
●Orbital arteriovenous malformation.
TREATMENT
Ocular
●Topical lubrication.
●Intraocular pressure lowering agents.
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Disorders Cardiovascular7 SECTIONand Hematologic •
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b |
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FIGURE 80.1. External photograph demonstrating arterialization (corkscrew appearance) of conjunctival vessels. The lateral digital subtraction angiogram of the right common carotid artery in early arterial phase demonstrates immediate dense contrast filling of the cavernous sinus (arrowhead) with drainage anteriorally through the superior ophthalmic vein (straight arrow) and posteriorally through the inferior petrosal sinus (curved arrow).
Medical
●Intermittent self-manual carotid artery compression.
Stereotactic radiosurgery Direct cavernous sinus surgery
Endovascular embolization (recommended therapy of choice)
●Transarterial route.
●Transvenous route.
●Superior ophthalmic vein route.
Complications of endovascular embolization therapy
●Carotid artery occlusion resulting in ipsilateral cerebral hemisphere ischemia.
●Transient worsening of ocular and orbital manifestations.
●Partial closure of fistula with persistent posterior venous drainage and cortical venous arterialization.
COMMENTS
The clinical manifestations of direct and dural carotid cavernous fistulas may overlap with the signs and symptoms being more dramatic in direct fistulas. All direct carotid cavernous sinus fistulas should be treated. In contrast dural fistulas can often be observed expectantly and in many cases may close spontaneously or after a diagnostic angiogram.
REFERENCES
Barrow DL, Spector RH, Braun IF, et al: Classification and treatment of spontaneous carotid-cavernous sinus fistulas. J Neurosurg 62(2):248– 256, 1985.
Goldberg RA, Goldey SH, Duckwiler G, Vinuela F: Management of cavernous sinus-dural fistulas. Indications and techniques for primary embolization via the superior ophthalmic vein. Arch Ophthalmol 114(6):707–714, 1996.
Grove AS, Jr: The dural shunt syndrome. Pathophysiology and clinical course. Ophthalmology 91(1):31–44, 1984.
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Miller NR: Carotid-cavernous sinus fistulas. In: Miller NR, Newman NJ, Biousse V, Kerrison JB, eds: Walsh and Hoyt’s clinical neuroophthalmology. 6th edn. Baltimore, Williams & Wilkins, 2005:2263–2296.
Sergott RC, Grossman RI, Savino PJ, et al: The syndrome of paradoxical worsening of dural-cavernous sinus arteriovenous malformations. Ophthalmology 94(3):205–212, 1987.
Tsai Y-F, Chen L-K, Su C-T, et al: Utility of source images of three dimensional time-of-flight magnetic resonance angiograpy in the diagnosis of indirect carotid-cavernous sinus fistulas. J Neuro-Ophthalmol 24:285–289, 2004.
81 SICKLE CELL RETINOPATHY 282.60
Hon-Vu Q. Duong, MD
Las Vegas, Nevada
ETIOLOGY/INCIDENCE
Sickle cell hemoglobinopathy encompasses a group of inherited genetic disorders, which cause erythrocytes to become sickled and affect multiple organ systems. The rigid sickled erythrocytes lead to vascular occlusion, which results in retinal hypoxia, ischemia, infarction, detachment, and neovascularization.
In sickle cell anemia (SS disease), the amino acid substitution valine for glutamate occurs on the β-chain at the sixth position. This substitution, combined with conditions that may promote sickling triggers the deoxygenated Hb S to polymerize, making the erythrocyte rigid. This rigidity is partially responsible for the vasoocclusion. Vasoocclusion is also in part due to the interaction between sickled cells and the vascular endothelium with the end result of vascular stasis, hemolysis, and vasoocclusion.
In the United States, sickle cell anemia primarily occurs in the black population, with approximately 0.2% of African-
American children afflicted by this disease. The prevalence in adults is lower because of the decrease in life expectancy. Sickle cell anemia is a homozygous-recessive disorder.
Sickle cell C disease is the second most common form, resulting from amino acid substitution of lysine for glutamic acid, and commonly seen in West African populations. Sickle cell thalassemia is the third most common form of sickle cell disease.
COURSE/PROGNOSIS
Systemic disease associated with sickle cell anemia is more common and more severe than ocular disease. Sickle cell C disease and sickle cell thalassemia tend to have mild systemic manifestations however, ocular manifestations can be severe.
Prognosis is fair to good if consistent follow-up care is maintained with both an internist/hematologist and an ophthalmologist.
DIAGNOSIS
Clinical signs and symptoms
Patients with a history of sickle cell anemia should undergo a dilated fundus exam based on retinal findings. Changes in the posterior segment are divided into 4 major categories: optic disc changes, macular changes, nonproliferative retinal changes, and proliferative retinal changes.
Optic disc
Intravascular occlusions primarily affect the small vessels on the surface of the optic disc and appear as dark red spots or clumps. They are often called the disc sign of sickling. They are self-limiting and do not produce any appreciable visual symptoms.
Macula
Vascular occlusion can lead to complete loss of vision or can lead to central or paracentral scotoma. A macular depression may be seen. Proliferative findings in the macular include macula hole, macula traction, enlarged segments of terminal arterioles, hairpin-shaped vascular loops, and abnormal foveal avascular zone.
Nonproliferative sickle cell retinopathy
While abnormal, nonproliferative changes are generally asymptomatic and do not require treatment. The nonproliferative changes include:
●venous tortuosity — common but not pathognomonic for sickle cell disease,
●salmon patch hemorrhage — intraretinal hematoma, found in the periphery, and confined to the neural retina,
●black sunburst — a pigmented chorioretinal scar, usually found in the periphery. These scars appear round or ovoid with stellate or speculate borders and often associated with iridescent spots,
●angiod streaks — breaks in Bruch membrane and appeared as pigmented striae that lie under the retinal vessels.
Proliferative retinopathy
Stage I — Peripheral arteriolar occlusion: areas of retinal ischemia secondary to nonperfusion become an abnormal grayish brown color.
FIGURE 81.1. Sickle cell retinopathy.
Stage II — Arterioilar-venular anastomoses: shunting of blood from the occluded arterioles to the nearest venules. Often difficult to view by ophthalmoscopy an FA can demonstrate arteriovenous anastomoses that do not leak dye.
Stage III — Neovascular proliferation: classic finding for stage IIII is the ‘sea fan –neovascularization’ lesion. On FA, sea fan lesions leak profusely (Figure 81.1).
Stage IV — Vitreous hemorrhage: it may be spontaneous secondary to vitreous collapse and/or traction of the adherent neovascular tissue.
Stage V — Retinal Detachment: detachments may be rhegmatogenous and/or tractional.
Differential diagnosis
●BRVO CRVO.
●Eales disease.
●Hypertension.
●Retinopathy of prematurity.
●Proliferative diabetic retinopathy.
●Sarcoidosis.
TREATMENT
Medical
This condition is treated by an internist or hematologist.
Surgical/Ocular
The primary goal in treating proliferative sickle cell retinopathy is to minimize or eliminate neovascularization. Although treatments are not indicated for stages I and II, most advocate treatment with stage III.
Laser photocoagulation
It is relatively safe and one of the more commonly used therapeutic modality. Different techniques have been advocated and include scatter or feeder vessel photocoagulation.
Retinal cryotherapy
Cryotherapy often is limited to cases with cloudy ocular media. Single freeze-thaw and triple freeze-thaw have been advocated in treating PSR.
Vitrectomy
Vitrectomy is indicated in cases of nonresolving vitreous hemorrhage and retinal detachment.
Disease Cell Sickle • 81 CHAPTER
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Disorders Cardiovascular7 SECTIONand Hematologic •
COMPLICATIONS
Anterior segment ischemia
●The following measures can decrease complications.
●Preoperative partial exchange transfusion.
●Administer local anesthesia, stellate ganglion block.
●Cycloplegic (parasympathomimetics).
●Decrease IOP and should be kept less than 25 mmHg, preoperatively, intraoperatively, and postoperatively.
●Supplemental oxygen.
Recurrent retinal detachment
Hyphema
Neovascular glaucoma
COMMENTS
Early detection and treatment may help decrease the retinal complications. Special concern should include repeated blood transfusion, hyphema, and scleral buckling. Ophthalmic care is determined by the proliferative stage. Patients should be well informed of their current and potential long-term complications. These patients are strongly encouraged to enroll at a local or regional sickle cell clinic along with providing these patients with local support group. Patients with diagnosed sickle cell disease should seek genetic counseling prior to starting a family.
REFERENCES
Andreoli TE, et al: Disorder of red cells. In: Cecil’s essentials of medicine. 4th edn. 1997:383–387.
Asdourian GK: Sickle cell retinopathy. In: Albert DM, Jakobiec FA, eds. Principles and practice of ophthalmology. 1994:II:1006–1018.
Beutler E: Disorders of hemoglobin. In: Fauci AS, et al, eds: Harrison’s principle of internal medicine. 14th edn. 1998:645–652.
Bunn HF: Pathogenesis and treatment of sickle cell disease. New Engl J Med 337(11):762–769, 1997.
Fekrat S, Lutty G, Goldberg M: Hemoglobinopathies. In: Guyer D, et al: Retina-vitreous macula. 1999:I:438–458.
Ho AC: Hemoglobinopathies. In: Yanoff, M, Duker, JS, eds. Ophthalmology. 2nd edn. Mosby, 2004:Ch119:891–895.
Yanoff M, Fine BS: Sickle cell disease. In: Ocular pathology. 4th edn. 1996:377–378.
thalassemias are the most common single-gene problem in humans. The chromosomal abnormalities can result in total gene deletion, rearrangements of genetic loci, mutations that impair transcription, defects in the processing of genetic information, and errors in the translation of RNA. In the past, these disorders had a variety of historic names (Cooley’s anemia, thalassemia major, thalassemia minor, etc.). In an attempt to include all the manifestations of this disorder, a nomenclature related to the involved polypeptide chain has become popular (alpha-thalassemia for alpha polypeptide chain abnormalities, beta-thalassemia for beta polypeptide chain abnormalities, etc.).
The clinical manifestations of this disorder are the results of inadequate globin production and the accumulation of blood products. The clinical features are diverse and can range from asymptomatic states to death from anemia. The most common clinical characteristic of the thalassemias is the development of a hypochromic microcystic anemia. However, in some patients, the pathologic changes represent such a small fraction of total globin synthesis that this abnormality is difficult to measure.
In general, when a patient has one thalassemia gene and one normal gene, the disorder is called thalassemia trait (thalassemia minor in the older literature) and a relatively mild anemia is present. When two similar genes are present, there is a more severe impairment of hemoglobin synthesis and a more severe anemia (thalassemia major in the older literature). In addition, it is possible to describe the thalassemias in regard to the rate of hemoglobin polypeptide chain synthesis. Some recent publications use this to specify the relative amount of hemoglobin synthesis impairment and imply this information (i.e. severe, mild and silent form of thalassemia) is of greater clinical value than the other nomenclatures.
The most common variety of thalassemia was described by Cooley and Lee in 1925. It is caused by a defect in the rate of synthesis of the beta-polypeptide chain of hemoglobin A. This abnormality results in a relative increase in the levels of hemoglobin A2 and hemoglobin F, along with the development of a microcystic hypochromic anemia. As the years progress, splenomegaly, hepatomegaly and discoloration of the skin and sclera occur. At one time, this particular disorder was thought to have a specific geographic distribution that extended from the Mediterranean through the Middle East, India and Southeast Asia. Although there is a relatively high gene frequency in those areas (it can range from 2.5% to 15% in those regions), it has been found that the thalassemias have a worldwide distribution.
82 THE THALASSEMIAS 282.4
Stephen S. Feman, MD, FACS
St. Louis, Missouri
Levent Akduman, MD
St. Louis, Missouri
Ozgur Yalcinbayir, MD
St. Louis, Missouri
The thalassemias are a group of hereditary disorders characterized by decreased rates of hemoglobin polypeptide chain synthesis. They represent the clinical features of a series of pathologic alleles on chromosome 11 and 16. As a group, the
COURSE/PROGNOSIS
Infants are born free of anemia because of prenatal hemoglobin F production. In most patients, the clinical manifestations are first identified at about the 6th month of life. Without treatment, 80% of the patients with the classic form of this disorder will die within 5 years. In these young infants, the most common associated clinical features consist of pallor, irritability, growth retardation, abdominal swelling and jaundice. Transfusions to prevent the associated anemias have become a treatment standard.
Ocular or periocular manifestations
Conjunctiva
Focal regions of dilated and turtuous vessels.
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Retina
Vascular tortuosity; pigmented chorioretinal scars (black sunburst pattern); iridescent intraretinal deposits; focal arterial occlusions; central retinal vein occlusion; neovascularizations; hemorrhages; angioid streaks which may be associated with subretinal neovascularization; macular pucker; and macular ischemia.
Vitreous
Hemorrhages.
THERAPY
Systemic
Transfusions to prevent the symptoms of anemia have been the standard of treatment for many years. In time, such therapy will result in an iron overload and hemosiderosis; this complication had been a common cause of death for these patients. However, with the use of iron chelators, such as deferoxamine and desferrioxamine, this danger is lessened. Nevertheless, splenomegaly can be a major problem for such patients and may need to be resolved with a splenectomy.
Ocular
The most serious threats to vision occur in patients with thalassemia and sickle cell trait. Such patients develop multifocal areas of peripheral retinal neovascularization that result in vitreous hemorrhages. The vessels feeding and draining the neovascular growth can be identified by fluorescein angiography, and photocoagulation to occlude these vessels can prevent such hemorrhages. Then, the surrounding area of ischemic retina can be treated with a scatter photocoagulation pattern to reduce the stimulus for recurrent neovascularization and to prevent future problems in that retinal region.
Precautions
Ocular complications indicate, in most cases, that the patient has a combination of thalassemia and some other hemoglobin abnormality. The treatment of the ocular manifestations associated with the other hemoglobin abnormality offers the greatest visual benefit to most patients. In addition, patients requiring frequent blood transfusions may show signs of retinal toxicity from the iron accumulation or from the desferrioxamine use. The clinical features of this type of retinal toxicity include night blindness, visual field defects and ERG changes.
COMMENTS
Whenever an intraocular hemorrhage, visual field defect, or retinal neovascular change is identified, one must search for an additional hemoglobin abnormality. If found, the treatment should be directed to the ocular and systemic manifestations of the other co-existing hemoglobinopathy to prevent additional visual loss.
Regular, or yearly, ophthalmic examinations are recommended for patients with the thalassemias in order to detect and treat possible ocular complications and to monitor the potential iron toxicity.
REFERENCES
Aessopos A, Farmakis D, Karagiorga M, et al: Pseudoxanthoma elasticum lesions and cardiac complications as contributing factors for strokes in beta-thalassemia patients. Stroke 28(12):2421–2424, 1997.
Aessopos A, Voskaridou E, Kavouklis E, et al: Angioid streaks in sicklethalassemia. Am J Ophthalmol 117(5):589–592, 1994.
Al-Hazzaa S, Bird AC, Kulozik A, et al: Ocular findings in Saudi Arabian patients with sickle cell disease. Br J Ophthalmol 79(5):457–461, 1995.
Carney MD, Jampol LM: Epiretinal membranes in sickle cell retinopathy. Arch Ophthalmol 105(2):214–217, 1987.
Comings DE: Thalassemia. In: Williams WJ, Beutler E, Lichtman MA, et al, eds: Hematology. New York, Mc Graw-Hill, 328–345, 1972.
Condon PI, Serjeant GR: Ocular findings in sickle cell thalassemia in Jamaica. Am J Ophthalmol 74:1105–1109, 1972.
Cooley TB, Lee P: A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr Soc 37:29–35, 1925.
Davies SC, Marcus RE, Hungerford JL, et al: Ocular toxicity of high-dose intravenous desferrioxamine. Lancet 2(8343):181–184, 1983.
Dennerlein JA, Lang GE, Stahnke K, et al: Ocular findings in Desferal therapy. Ophthalmologe 92(1):38–42, 1995.
Feman SS, Westrich DJ: Macular arteriolar occlusions in sickle cell betathalassemia. Am J Ophthalmol 101:739–740, 1986.
Goldberg MF, Charache S, Acacio I: Ophthalmologic manifestations of sickle cell thalassemia. Arch Intern Med 128:33–39, 1971.
Gupta A, Agarwal A, Bansal RK, et al: Ischaemic central retinal vein occlusion in the young. Eye 7(Pt 1):138–142, 1993.
Kinsella FP, Mooney DJ: Angioid streaks in beta thalassaemia minor. Br J Ophthalmol 72(4):303–304, 1988.
Magli A, Fusco R, Mettivier V, Pisapia R: Ocular manifestations in thalassemia minor. Ophthalmologica 184:139–146, 1982.
Theodossiadis G, Ladas I, Koutsandrea C, et al: Thalassemia and macular subretinal neovascularization. J Fr Ophtalmol 7(2):115–118, 1984.
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