The thalassemias are the most common monogenic diseases on a worldwide basis. In 2 of the phenotypes, thalassemia major and thalassemia intermedia, severe anemia may develop leading to a variety of complications, including hepatosplenomegaly, expansion of medullary spaces, extramedullary hematopoiesis, and increased iron absorption and caloric needs (1). In extreme cases, extramedullary hematopoietic tumors may develop. Thalassemia intermedia is less severe than the major form and may require blood transfusions later in life (1,2). Spinal cord compression secondary to extramedullary hematopoiesis in the vertebral canal has been reported in patients with thalassemia intermedia (3,4). We describe optic neuropathy as a sequela of thalassemia.
A 21-year-old man was referred to the ophthalmology clinic for headache and blurred vision occurring over the past year. His headache was global, constant, and sustained, gradually increasing in intensity and interfering with sleep for the past few weeks. He was known to have beta-thalassemia intermedia and had received intermittent blood transfusions since 17 years. An older brother and sister also had thalassemia and both died at 19 and 20 years of age, respectively, secondary to cardiopulmonary failure.
On examination, visual acuity was counting fingers at 2 m, right eye, and hand motions, left eye. There was a left relative afferent pupillary defect. The patient had a 30 prism-diopter left exotropia with full eye movements. Ophthalmoscopy revealed slightly elevated diffusely pale optic discs with sharp borders and peripapillary changes (Paton lines) consistent with chronic optic disc edema. Spontaneous venous pulsations were not seen. Slight retinal venous tortuisity was noted with mild granular appearance in both maculae.
The patient was short in stature (height = 145 cm) with typical thalassemic facies, including frontal bossing, hypertelorism, depressed nasal bridge, and prominent maxillae. He had hepatosplenomegaly, and secondary sexual characteristics were not developed.
Hemoglobin electrophoresis results were HbA: 28.6%, HbF: 65.7%, and HbA2: 5.7%. Complete blood count showed hemoglobin of 8.3 mg/dL (normal: 14-18 mg/dL), hematocrit of 27 (normal: 39-52), with anisocytosis, microcytosis, hypochromia, and nucleated red blood cells (RBCs) (10 per 100 RBCs). Plain skull films showed widening of diploe, and orbital and brain CT showed markedly enlarged medullary bone spaces (Fig. 1). The minimum optic canal diameter was 3.0 mm. Brain MRI (Fig. 2A) revealed hyperplastic bone marrow tissue arising from clivus, filling the sphenoid sinus, pituitary fossa, and suprasellar and prepontine cisterns. This hematopoietic tissue almost totally obliterated the optic foramina and compressed the optic nerves. There was also massive expansion of the diploic space of the calvarium with compression of the intracranial contents (Fig. 2B). Additional MRI images demonstrated relative dilation of the third ventricle, atria, and temporal horns of the lateral ventricles consistent with hydrocephalus due to compression of the sylvian aqueduct.
Treatment was begun with regular blood transfusions and 250 mg of acetazolamide 3 times daily. The patient and his guardians refused surgical intervention and radiotherapy.
Three months later, he reported decreased headaches but no change in vision. After 13 months, visual acuity was counting fingers at 2 m, right eye and at 0.5 m, left eye. Marked bilateral optic atrophy was present. Further evaluation and treatment were declined by the patient.
Ineffective erythropoiesis in thalassemia results in the expansion of medullary spaces and extramedullary hematopoiesis with the formation of hematopoietic tumors in extreme cases. Marrow expansion may cause craniofacial deformities, pathologic fractures, and neurologic symptoms (1,2). Extramedullary hematopoiesis has been reported to occur in the vertebral canal, compressing the spinal cord (3-5). This is a medical emergency usually requiring immediate local surgical decompression followed by radiation therapy. Blood transfusion will slow these complications by halting erythropoiesis (2,3,5).
A number of factors led to optic nerve involvement and profound visual loss in our patient. First is the direct compressive effect of extramedullary hematopoietic tissue, arising from clivus and sphenoid bones, upon the optic nerves and chiasm. Second, the optic nerves were also compressed by narrowed optic canals resulting from expansion of medullary spaces of the sphenoid bone. Third, compression of the intracranial contents by expanded diploe led to raised intracranial pressure and the fundus findings of chronic papilledema. Finally, it is possible that the enlarged diploe may have compressed dural sinuses, impairing venous drainage and contributing to increased intracranial pressure.
To the best of our knowledge, only 3 cases of optic atrophy secondary to expanded hematopoietic tissue in thalassemia have been reported. Sorcinelli et al (6) described a patient with thalassemia intermedia who developed bilateral optic atrophy resulting from narrowing of optic canals secondary to expansion of hematopoietic tissue. The patient received a variety of treatment, including corticosteroids, blood transfusions, erythropoietin, and hyperbaric oxygen, and vision stabilized at 20/20, right eye, and 20/40, left eye. Aarabi et al (7) reported a case with thalassemia intermedia who developed bilateral optic atrophy secondary to compressive effects of parasellar hematopoietic mass. At presentation visual acuity was counting fingers at 1 m, right eye, and counting fingers at 0.5 m, left eye. The patient underwent partial resection of the tumor combined with monthly blood transfusions and low-dose radiotherapy. Final acuity was counting fingers at 2 m, right eye and 1 m, left eye. Ittipunkul et al (8) reported a 14-year-old girl with beta-thalassemia who presented with decreased vision of 2/60, right eye, and 5/60, left eye and optic atrophy. A soft tissue mass in the ethmoid and sphenoid sinuses led to compression of the optic nerves. The patient was treated with blood transfusions and a course of radiotherapy (1300 cGy in 6 fractions) for more than 1 week. One week later, vision improved to 6/60 in each eye.
Therapeutic options continue to evolve in the management of thalassemia. Blood transfusions alone may, in some cases, resolve the symptomatology and should be considered as the first step in management of these patients. Surgery and radiotherapy may also be beneficial in selected cases. Bone marrow transplantation and gene therapy offer the possibility of curative treatment in the future. We recommend periodic comprehensive ophthalmic examinations in thalassemia intermedia patients, particularly for those receiving irregular blood transfusions.
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© 2011 Lippincott Williams & Wilkins, Inc.
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