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Blindness From Bad Bones
SURVEY OF OPHTHALMOLOGY VOLUME 43 • NUMBER 6 • MAY–JUNE 1999
AFTERIMAGES JONATHAN WIRTSCHAFTER, EDITOR
Blindness From Bad Bones R. MICHAEL SIATKOWSKI, MD,1 NANCY F. VILAR, MD, PhD,1 LINDA STERNAU, MD,2 AND C. GENE COIN, MD3 1 Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, 2Department of Neurosurgery, Mount Sinai Hospital, Miami Beach, and 3Department of Radiology, Veterans’ Administration Hospital/ University of Miami School of Medicine, Miami, Florida, USA
Abstract. Progressive visual loss is the most common neurologic finding in osteopetrosis. Several mechanisms may explain this phenomenon, including compression of the optic nerves caused by bony overgrowth of the optic canals and retinal degeneration. We report a child with osteopetrosis and progressive visual loss, even though patent optic canals were demonstrated by computed tomography and digital holography. This patient’s visual loss was caused by increased intracranial pressure secondary to obstruction of cerebral venous outflow at the jugular foramen. This case points to the importance of a full evaluation of the skull base foramina in the diagnostic workup of visual loss in patients with osteopetrosis. (Surv Ophthalmol 43:487–490, 1999. © 1999 by Elsevier Science Inc. All rights reserved.) Key words. digital holography
•
intracranial pressure
Case Report. A 5-year-old white boy presented with a 2-year history of progressive visual loss. Postnatally, motor skills were delayed, and during his first years of life he suffered multiple fractures, chronic anemia, and hepatosplenomegaly. Osteopetrosis was diagnosed, and the patient was treated with interferon gamma. One year before he came to us, the patient had been placed on synthetic human growth hormone because of persistent small stature. He developed chronic headaches and underwent lumbar puncture, which revealed an elevated opening pressure. He was presumed to have a growth hormone– related rise in intracranial pressure, and the medication was discontinued. The headaches resolved, and motor, cognitive, and hearing development progressed normally. He was referred for a neuro-ophthalmology evaluation when he had visual difficulties at school.
•
jugular stenosis
•
osteopetrosis
Examination revealed visual acuities of 20/200 in the right eye (OD) and 20/150 in the left eye (OS). An afferent pupillary defect was present in the right eye. Motility was full, with congenital nystagmus and a right exotropia of 20 prism diopters. Funduscopic examination showed bilateral disk pallor. The patient had prominent frontal bossing (Fig. 1) and an enlarged head, and was at the fifth percentile for height and weight. He was treated with glasses and patching for possible amblyopia, but visual acuity did not improve. Six weeks later visual acuity was 20/300 OD and 20/200 OS. As seen by quantitative A-scan echography, both optic nerve sheath complexes were enlarged to 5.8 mm with a positive 308 test, indicating increased subarachnoid fluid. Brain computed tomography (CT) showed thickening of the skull and narrowing of the optic canals bilaterally; however, the canals remained 487
© 1999 by Elsevier Science Inc. All rights reserved.
0039-6257/99/$19.00 PII S0039-6257(99)00048-X
488
Surv Ophthalmol 43 (6) May–June 1999
SIATKOWSKI ET AL
Fig. 2. Coronal brain CT. Skull thickening and narrowing of the optic canals bilaterally (arrows).
Fig. 1. Facial view shows prominent frontal bossing, venous distension (arrow), and enlarged head.
patent (Figs. 2 and 3). Baseline electroretinogram (ERG) was recommended, but the patient’s family refused. In an attempt to improve visual function, optic nerve sheath fenestration was performed. Postoperatively, visual acuity improved to 20/150 OD and 20/100 OS. One year later, visual acuity began to drop again, to 3/200 OD and 4/100 OS, and was associated with nausea, vomiting, and headaches. Echography again showed enlargement of both optic nerves with a positive 308 test.
Fig. 3. Coronal brain CT. Optic canals narrowed but patent.
Further workup was done when visual loss recurred. Digital holography disclosed patent optic canals. (To view the hologram, please visit the Survey of Ophthalmology home page at http://www.elsevier.com/ locate/survopthal and select the link to “Blindness From Bad Bones.”) Unlike computer-generated images, digital holography allows for production of true three-dimensional images in space.5 This method uses a series of interference patterns produced from CT or magnetic resonance imaging (MRI) sections, which are optically imprinted on special holographic film. When viewed with a special lightbox, the resultant image is a true hologram that faithfully reproduces the subject as a semitransparent solid object. Thus, a life-sized image may be observed from any aspect. Measurements and observations from this hologram are precisely accurate, limited only by the input sections. Brain MRI (Fig. 4) showed extensive thickening of the calvarium with low signal of the marrow, compression of the convexity of the brain, and tonsilar herniation. The pons was compressed against the clivus anteriorly. The suboccipital bone biopsy showed thickening and sclerosis of the cortex, with overgrowth of the osteoid filling of the medullary cavity (Fig. 5). Lumbar puncture revealed an opening pressure of 45 cm H2O with normal results of chemistry studies and no cells. Cerebral angiography (Fig. 6) showed bilateral venous obstruction at the level of the sigmoid sinus–jugular bulb junction. Venous pressures in the transverse sinus and the jugular vein demonstrated a 10-mm gradient, indicating significant obstruction at the level of the jugular bulb. There were also increased venous collaterals, consistent with obstructive disease. At this juncture, the family agreed to an ERG, which revealed a severe reduction in both rod and cone function bilaterally. Visual evoked responses were nonrecordable in both eyes.
489
BLINDNESS FROM BAD BONES
Fig. 4. Sagittal brain MRI. Diffuse thickening of the calvarium with low signal of the marrow (white triangle). There is compression of the convexity of the brain, tonsilar herniation (black arrow), and clivopontine compression (white arrowhead).
Because of the progressive visual loss associated with increased intracranial pressure, a ventriculoperitoneal shunt procedure was performed, with subsequent improvement of visual acuity to 20/150 in both eyes. The patient was visually and neurologically stable for 1 year. He later developed sleep apnea, ataxia, nausea, and vomiting. He was found to have progressive downward cerebellar tonsilar herniation. He underwent a suboccipital craniotomy and cervical laminectomy to decompress this Chiari-type anomaly. However, ERG results confirmed that retinal degeneration also played a role in the progressive visual loss of this patient. Unfortunately, despite normal intracranial pressure, visual acuity continued to decline and 1 year later was 1/160 OD and 1/200 OS. Because of progression of osteopetrosis, the pa-
Fig. 6. Conventional angiography demonstrates bilateral venous obstruction at the level of the sigmoid sinus jugular–bulb junction (black arrow) with increased cervical collateral veins (arrowhead).
Fig. 5. Histopathology of bone marrow shows sclerosis of the cortex with overgrowth of the osteoid, filling the medullary cavity (black arrow).
tient underwent bone marrow transplant, but he died of sepsis in the fall of 1998.
Discussion Osteopetrosis is a metabolic bone disorder characterized by increased skeletal mass caused by defective bone resorption. Progressive visual loss is the most common neurologic finding. The autosomal dominant type of osteopetrosis is often mild and asymptomatic, with a wide variety of presentations, ranging from lumbar bone pain to cranial nerve palsies. Autosomal recessive type 1 disease has a frequency of 5–10 per million births. Autosomal recessive type 2 disease presents with renal tubular acidosis, calcification of the basal ganglia, and deficient carbonic anhydrase. Type 3 disease (which most closely represents our patient) is similar, and is characterized by short stature, recurrent fractures, osteomyelitis, and anemia. There are several mechanisms that produce visual loss in osteopetrosis. Compression of the optic nerves because of bony overgrowth of the optic canals1,3,4 occurs most commonly, but cerebral venous outflow obstruction resulting in raised intracranial pressure,11 hydrocephalus, and long-standing papilledema can lead to optic atrophy as well.6,11 Retinal dysfunction associated with decreased ERG amplitudes,12 degeneration of rods and cones, degeneration of the outer nuclear layer, and atrophy and gliosis of the ganglion cell layer9 are also well documented, as are neuronal storage diseases associated with lysosomal enzyme deficiency and degenerative retinal changes.2,7 The most important tool in the diagnosis of osteopetrosis is radiologic evaluation, which shows diffuse
490
Surv Ophthalmol 43 (6) May–June 1999
bony sclerosis and an increase in the density of the diaphyseal regions of the growing bone. Metabolic studies reveal elevated acid phosphatase, but normal serum calcium, phosphorus, and alkaline phosphatase. Histology demonstrates thickened bony cortex, marrow filled with spongiosa, fewer than normal osteoblasts, and flat osteoclasts in all stages of development. From a systemic standpoint, therapeutic options include calcitriol or interferon gamma, both of which increase bone resorption. Interferon improves hematopoiesis and leukocyte function as well.10 Bone marrow transplantation to replenish normal osteoclasts has a success rate of 50%.8,13 Surgical management of visual loss includes canalicular decompression, shunting procedures, and optic nerve sheath fenestration. Because of the variety of mechanisms responsible for the visual loss in this disorder, a variety of diagnostic tests (orbital ultrasound, brain CT, brain MRI, cerebral angiography, MR and conventional venography, digital holography, and ERG) are generally necessary to clarify the relative contribution of each mechanism in each patient. When such a patient is encountered, we recommend a brain CT, ERG, and lumbar puncture as part of an initial workup. Results of the ERG will allow the examiner to determine if there is a component of retinal degeneration (which is currently untreatable) in the patient’s visual loss. If the patency of the optic foramen is unclear from the CT, digital holography can provide valuable information for the consideration of foraminal decompression. However, this procedure should not be undertaken without considering the possibility of venous obstruction at the base of the skull. If the lumbar puncture yields an elevated opening pressure, further imaging of the base of the skull and/or venography will be necessary. Although quantitative A-scan echography is most helpful for demonstrating excess subarachnoid fluid around the optic nerve (as occurs in elevated intracranial pressure), this technique is not available in many institutions. Our case is unique in that before the development of optic foramen stenosis (the most common cause of visual loss in osteopetrosis), the patient presented with increased intracranial pressure. One cause of this is undoubtedly the diminished intracranial volume and compression of the cranial contents with bony overgrowth. However, a second, and treatable, cause of raised intracranial pressure is venous outflow obstruction at the level of a narrowed jugular foramen; the existence of this phenomenon in osteopetrosis is neither well known nor well described in the literature. (The prominence of this patient’s forehead veins may indeed be a sign of venous outflow obstruction.) This condition responded to central spinal fluid shunting and, ultimately, a posterior fossa decompression. Although the progressive reti-
SIATKOWSKI ET AL
nal degeneration resulted in blindness, we were able to preserve functional vision for several years of this patient’s short life. As the success of bone marrow and stem cell transplantation in the treatment of osteopetrosis improves, preservation of vision in these patients for as long as possible will become even more important.
Summary We have presented a case of progressive visual loss in osteopetrosis and have reviewed the mechanisms behind this phenomenon. Our report demonstrates the necessity of a full evaluation of the skull base foramina before planning bilateral optic foraminal decompression, as well as the unique ability of digital holography to assist in assessing the anatomic status of these patients.
References 1. Al-Mefty O, Fox J, Al-Rodham N, Dew J: Optic nerve decompression of osteopetrosis. Neurosurgery 68:80–84, 1988 2. Ambler MW, Trice J, Grauerholz J, O’Shea P: Infantile osteopetrosis and neuronal storage disease. Neurology 33:437– 441, 1983 3. Ellis P, Jackson WE: Osteopetrosis: A clinical study of the optic nerve involvement. Am J Ophthalmol 52:943–953, 1962 4. Haines SJ, Erickson DL, Wirtschafter JD: Optic nerve decompression for osteopetrosis in early childhood. Neurosurgery 23:470–475, 1988 5. Hart SJ, Dalton MN: Display holography for medical tomography. Practical Holography IV, Los Angeles, Jan 18–19, 1990. Proc SPIE 1212:116–135. 6. Hoyt CS, Billson FA: Visual loss in osteopetrosis. Am J Dis Child 33:955–958, 1979 7. Jagadha V, Halliday WC, Becker LE, Hinton D: The association of infantile osteopetrosis and neuronal storage disease in two brothers. Acta Neuropathol 75:233–240, 1988 8. Kaplan FS, August CS, Fallon MD, et al: Successful treatment of infantile malignant osteopetrosis by bone-marrow transplantation: A case report. J Bone Joint Surg Am 70:617–623, 1988 9. Keith CG: Retinal atrophy in osteopetrosis. Arch Ophthalmol 79:234–241, 1968 10. Key LL Jr, Rodriguiz RM, Willi SM, et al: Longterm treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 332:1594–1599, 1995 11. Klintworth G: The neurologic manifestations of osteopetrosis. Neurology 13:512, 1963 12. Ruben JB, Morris RJ, Judisch GF: Chorioretinal degeneration in infantile malignant osteopetrosis. Am J Ophthalmol 110:1–5, 1990 13. Solh H, Da Cuhna AM, Giri N, et al: Bone marrow transplantation for infantile osteopetrosis. J Pediatr Hematol Oncol 17:350–355, 1995
We thank Raymond Schulz for making the digital holographic image available through the Voxel Library of Digital Holography Images. Presented in part at the Annual Frank B. Walsh Society Meeting, March 23,1998, Orlando, Florida. Supported in part by an unrestricted Department of Ophthalmology research grant and a grant from Research to Prevent Blindness, New York, New York. The authors have no proprietary interest in the products or techniques discussed in this article. Reprints not available. Inquiries: R. Michael Siatkowski, MD, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.
AFTERIMAGES JONATHAN WIRTSCHAFTER, EDITOR
Blindness From Bad Bones R. MICHAEL SIATKOWSKI, MD,1 NANCY F. VILAR, MD, PhD,1 LINDA STERNAU, MD,2 AND C. GENE COIN, MD3 1 Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami School of Medicine, 2Department of Neurosurgery, Mount Sinai Hospital, Miami Beach, and 3Department of Radiology, Veterans’ Administration Hospital/ University of Miami School of Medicine, Miami, Florida, USA
Abstract. Progressive visual loss is the most common neurologic finding in osteopetrosis. Several mechanisms may explain this phenomenon, including compression of the optic nerves caused by bony overgrowth of the optic canals and retinal degeneration. We report a child with osteopetrosis and progressive visual loss, even though patent optic canals were demonstrated by computed tomography and digital holography. This patient’s visual loss was caused by increased intracranial pressure secondary to obstruction of cerebral venous outflow at the jugular foramen. This case points to the importance of a full evaluation of the skull base foramina in the diagnostic workup of visual loss in patients with osteopetrosis. (Surv Ophthalmol 43:487–490, 1999. © 1999 by Elsevier Science Inc. All rights reserved.) Key words. digital holography
•
intracranial pressure
Case Report. A 5-year-old white boy presented with a 2-year history of progressive visual loss. Postnatally, motor skills were delayed, and during his first years of life he suffered multiple fractures, chronic anemia, and hepatosplenomegaly. Osteopetrosis was diagnosed, and the patient was treated with interferon gamma. One year before he came to us, the patient had been placed on synthetic human growth hormone because of persistent small stature. He developed chronic headaches and underwent lumbar puncture, which revealed an elevated opening pressure. He was presumed to have a growth hormone– related rise in intracranial pressure, and the medication was discontinued. The headaches resolved, and motor, cognitive, and hearing development progressed normally. He was referred for a neuro-ophthalmology evaluation when he had visual difficulties at school.
•
jugular stenosis
•
osteopetrosis
Examination revealed visual acuities of 20/200 in the right eye (OD) and 20/150 in the left eye (OS). An afferent pupillary defect was present in the right eye. Motility was full, with congenital nystagmus and a right exotropia of 20 prism diopters. Funduscopic examination showed bilateral disk pallor. The patient had prominent frontal bossing (Fig. 1) and an enlarged head, and was at the fifth percentile for height and weight. He was treated with glasses and patching for possible amblyopia, but visual acuity did not improve. Six weeks later visual acuity was 20/300 OD and 20/200 OS. As seen by quantitative A-scan echography, both optic nerve sheath complexes were enlarged to 5.8 mm with a positive 308 test, indicating increased subarachnoid fluid. Brain computed tomography (CT) showed thickening of the skull and narrowing of the optic canals bilaterally; however, the canals remained 487
© 1999 by Elsevier Science Inc. All rights reserved.
0039-6257/99/$19.00 PII S0039-6257(99)00048-X
488
Surv Ophthalmol 43 (6) May–June 1999
SIATKOWSKI ET AL
Fig. 2. Coronal brain CT. Skull thickening and narrowing of the optic canals bilaterally (arrows).
Fig. 1. Facial view shows prominent frontal bossing, venous distension (arrow), and enlarged head.
patent (Figs. 2 and 3). Baseline electroretinogram (ERG) was recommended, but the patient’s family refused. In an attempt to improve visual function, optic nerve sheath fenestration was performed. Postoperatively, visual acuity improved to 20/150 OD and 20/100 OS. One year later, visual acuity began to drop again, to 3/200 OD and 4/100 OS, and was associated with nausea, vomiting, and headaches. Echography again showed enlargement of both optic nerves with a positive 308 test.
Fig. 3. Coronal brain CT. Optic canals narrowed but patent.
Further workup was done when visual loss recurred. Digital holography disclosed patent optic canals. (To view the hologram, please visit the Survey of Ophthalmology home page at http://www.elsevier.com/ locate/survopthal and select the link to “Blindness From Bad Bones.”) Unlike computer-generated images, digital holography allows for production of true three-dimensional images in space.5 This method uses a series of interference patterns produced from CT or magnetic resonance imaging (MRI) sections, which are optically imprinted on special holographic film. When viewed with a special lightbox, the resultant image is a true hologram that faithfully reproduces the subject as a semitransparent solid object. Thus, a life-sized image may be observed from any aspect. Measurements and observations from this hologram are precisely accurate, limited only by the input sections. Brain MRI (Fig. 4) showed extensive thickening of the calvarium with low signal of the marrow, compression of the convexity of the brain, and tonsilar herniation. The pons was compressed against the clivus anteriorly. The suboccipital bone biopsy showed thickening and sclerosis of the cortex, with overgrowth of the osteoid filling of the medullary cavity (Fig. 5). Lumbar puncture revealed an opening pressure of 45 cm H2O with normal results of chemistry studies and no cells. Cerebral angiography (Fig. 6) showed bilateral venous obstruction at the level of the sigmoid sinus–jugular bulb junction. Venous pressures in the transverse sinus and the jugular vein demonstrated a 10-mm gradient, indicating significant obstruction at the level of the jugular bulb. There were also increased venous collaterals, consistent with obstructive disease. At this juncture, the family agreed to an ERG, which revealed a severe reduction in both rod and cone function bilaterally. Visual evoked responses were nonrecordable in both eyes.
489
BLINDNESS FROM BAD BONES
Fig. 4. Sagittal brain MRI. Diffuse thickening of the calvarium with low signal of the marrow (white triangle). There is compression of the convexity of the brain, tonsilar herniation (black arrow), and clivopontine compression (white arrowhead).
Because of the progressive visual loss associated with increased intracranial pressure, a ventriculoperitoneal shunt procedure was performed, with subsequent improvement of visual acuity to 20/150 in both eyes. The patient was visually and neurologically stable for 1 year. He later developed sleep apnea, ataxia, nausea, and vomiting. He was found to have progressive downward cerebellar tonsilar herniation. He underwent a suboccipital craniotomy and cervical laminectomy to decompress this Chiari-type anomaly. However, ERG results confirmed that retinal degeneration also played a role in the progressive visual loss of this patient. Unfortunately, despite normal intracranial pressure, visual acuity continued to decline and 1 year later was 1/160 OD and 1/200 OS. Because of progression of osteopetrosis, the pa-
Fig. 6. Conventional angiography demonstrates bilateral venous obstruction at the level of the sigmoid sinus jugular–bulb junction (black arrow) with increased cervical collateral veins (arrowhead).
Fig. 5. Histopathology of bone marrow shows sclerosis of the cortex with overgrowth of the osteoid, filling the medullary cavity (black arrow).
tient underwent bone marrow transplant, but he died of sepsis in the fall of 1998.
Discussion Osteopetrosis is a metabolic bone disorder characterized by increased skeletal mass caused by defective bone resorption. Progressive visual loss is the most common neurologic finding. The autosomal dominant type of osteopetrosis is often mild and asymptomatic, with a wide variety of presentations, ranging from lumbar bone pain to cranial nerve palsies. Autosomal recessive type 1 disease has a frequency of 5–10 per million births. Autosomal recessive type 2 disease presents with renal tubular acidosis, calcification of the basal ganglia, and deficient carbonic anhydrase. Type 3 disease (which most closely represents our patient) is similar, and is characterized by short stature, recurrent fractures, osteomyelitis, and anemia. There are several mechanisms that produce visual loss in osteopetrosis. Compression of the optic nerves because of bony overgrowth of the optic canals1,3,4 occurs most commonly, but cerebral venous outflow obstruction resulting in raised intracranial pressure,11 hydrocephalus, and long-standing papilledema can lead to optic atrophy as well.6,11 Retinal dysfunction associated with decreased ERG amplitudes,12 degeneration of rods and cones, degeneration of the outer nuclear layer, and atrophy and gliosis of the ganglion cell layer9 are also well documented, as are neuronal storage diseases associated with lysosomal enzyme deficiency and degenerative retinal changes.2,7 The most important tool in the diagnosis of osteopetrosis is radiologic evaluation, which shows diffuse
490
Surv Ophthalmol 43 (6) May–June 1999
bony sclerosis and an increase in the density of the diaphyseal regions of the growing bone. Metabolic studies reveal elevated acid phosphatase, but normal serum calcium, phosphorus, and alkaline phosphatase. Histology demonstrates thickened bony cortex, marrow filled with spongiosa, fewer than normal osteoblasts, and flat osteoclasts in all stages of development. From a systemic standpoint, therapeutic options include calcitriol or interferon gamma, both of which increase bone resorption. Interferon improves hematopoiesis and leukocyte function as well.10 Bone marrow transplantation to replenish normal osteoclasts has a success rate of 50%.8,13 Surgical management of visual loss includes canalicular decompression, shunting procedures, and optic nerve sheath fenestration. Because of the variety of mechanisms responsible for the visual loss in this disorder, a variety of diagnostic tests (orbital ultrasound, brain CT, brain MRI, cerebral angiography, MR and conventional venography, digital holography, and ERG) are generally necessary to clarify the relative contribution of each mechanism in each patient. When such a patient is encountered, we recommend a brain CT, ERG, and lumbar puncture as part of an initial workup. Results of the ERG will allow the examiner to determine if there is a component of retinal degeneration (which is currently untreatable) in the patient’s visual loss. If the patency of the optic foramen is unclear from the CT, digital holography can provide valuable information for the consideration of foraminal decompression. However, this procedure should not be undertaken without considering the possibility of venous obstruction at the base of the skull. If the lumbar puncture yields an elevated opening pressure, further imaging of the base of the skull and/or venography will be necessary. Although quantitative A-scan echography is most helpful for demonstrating excess subarachnoid fluid around the optic nerve (as occurs in elevated intracranial pressure), this technique is not available in many institutions. Our case is unique in that before the development of optic foramen stenosis (the most common cause of visual loss in osteopetrosis), the patient presented with increased intracranial pressure. One cause of this is undoubtedly the diminished intracranial volume and compression of the cranial contents with bony overgrowth. However, a second, and treatable, cause of raised intracranial pressure is venous outflow obstruction at the level of a narrowed jugular foramen; the existence of this phenomenon in osteopetrosis is neither well known nor well described in the literature. (The prominence of this patient’s forehead veins may indeed be a sign of venous outflow obstruction.) This condition responded to central spinal fluid shunting and, ultimately, a posterior fossa decompression. Although the progressive reti-
SIATKOWSKI ET AL
nal degeneration resulted in blindness, we were able to preserve functional vision for several years of this patient’s short life. As the success of bone marrow and stem cell transplantation in the treatment of osteopetrosis improves, preservation of vision in these patients for as long as possible will become even more important.
Summary We have presented a case of progressive visual loss in osteopetrosis and have reviewed the mechanisms behind this phenomenon. Our report demonstrates the necessity of a full evaluation of the skull base foramina before planning bilateral optic foraminal decompression, as well as the unique ability of digital holography to assist in assessing the anatomic status of these patients.
References 1. Al-Mefty O, Fox J, Al-Rodham N, Dew J: Optic nerve decompression of osteopetrosis. Neurosurgery 68:80–84, 1988 2. Ambler MW, Trice J, Grauerholz J, O’Shea P: Infantile osteopetrosis and neuronal storage disease. Neurology 33:437– 441, 1983 3. Ellis P, Jackson WE: Osteopetrosis: A clinical study of the optic nerve involvement. Am J Ophthalmol 52:943–953, 1962 4. Haines SJ, Erickson DL, Wirtschafter JD: Optic nerve decompression for osteopetrosis in early childhood. Neurosurgery 23:470–475, 1988 5. Hart SJ, Dalton MN: Display holography for medical tomography. Practical Holography IV, Los Angeles, Jan 18–19, 1990. Proc SPIE 1212:116–135. 6. Hoyt CS, Billson FA: Visual loss in osteopetrosis. Am J Dis Child 33:955–958, 1979 7. Jagadha V, Halliday WC, Becker LE, Hinton D: The association of infantile osteopetrosis and neuronal storage disease in two brothers. Acta Neuropathol 75:233–240, 1988 8. Kaplan FS, August CS, Fallon MD, et al: Successful treatment of infantile malignant osteopetrosis by bone-marrow transplantation: A case report. J Bone Joint Surg Am 70:617–623, 1988 9. Keith CG: Retinal atrophy in osteopetrosis. Arch Ophthalmol 79:234–241, 1968 10. Key LL Jr, Rodriguiz RM, Willi SM, et al: Longterm treatment of osteopetrosis with recombinant human interferon gamma. N Engl J Med 332:1594–1599, 1995 11. Klintworth G: The neurologic manifestations of osteopetrosis. Neurology 13:512, 1963 12. Ruben JB, Morris RJ, Judisch GF: Chorioretinal degeneration in infantile malignant osteopetrosis. Am J Ophthalmol 110:1–5, 1990 13. Solh H, Da Cuhna AM, Giri N, et al: Bone marrow transplantation for infantile osteopetrosis. J Pediatr Hematol Oncol 17:350–355, 1995
We thank Raymond Schulz for making the digital holographic image available through the Voxel Library of Digital Holography Images. Presented in part at the Annual Frank B. Walsh Society Meeting, March 23,1998, Orlando, Florida. Supported in part by an unrestricted Department of Ophthalmology research grant and a grant from Research to Prevent Blindness, New York, New York. The authors have no proprietary interest in the products or techniques discussed in this article. Reprints not available. Inquiries: R. Michael Siatkowski, MD, Dean A. McGee Eye Institute, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA.