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Congenital anomalies and acquired abnormalities of the optic nerve

Author
Karl C Golnik, MD, MEd
Section Editor
Evelyn A Paysse, MD
Deputy Editor
Carrie Armsby, MD, MPH

INTRODUCTION

The normal optic nerve head (optic disc) usually is round or oval and pink in color; typically it is flat or mildly elevated and has a central depression called the cup (picture 1). The horizontal diameter of the normal optic nerve is approximately 1.5 mm. The ratio between the cup and disc diameters is important to note because acquired optic nerve damage can cause cupping, an increase in the cup/disc ratio.

Optic nerve abnormalities can be categorized as congenital or acquired. Congenital optic nerve anomalies are distinguished by the appearance of the optic disc and surrounding retina. As a general rule, these anomalies are classified according to abnormalities of optic disc size or conformation and by the presence of abnormal tissue at the nerve head (pseudoswelling). Acquired abnormalities of the optic nerve are classified according to the reaction of the optic nerve to insult: cupping, swelling, and atrophy.

CONGENITAL ANOMALIES

Disc size — The optic nerve head may be absent (aplasia), small (hypoplasia), or large (megalopapilla).

Aplasia — Optic nerve aplasia is an extremely rare, nonhereditary occurrence of unknown etiology. It is characterized by complete lack of the optic nerve, disc, retinal nerve fiber layer, ganglion cells, and retinal vasculature [1,2]. Optic nerve aplasia typically is associated with a variety of other ocular malformations, including microphthalmia, cataract, anterior chamber angle malformation, retinal dysplasia, anterior coloboma (fissure or cleft of the iris or ciliary body), iris hypoplasia, and persistent fetal vasculature (formerly called persistent hyperplastic primary vitreous). Although individuals who are affected unilaterally usually are healthy otherwise, with rare exception, bilaterally affected individuals die shortly after birth [3,4].

Hypoplasia — Optic nerve hypoplasia is the most common congenital optic disc anomaly [5]. In a population-based study (1984-2008), the annual incidence was 2.4 per 100,000 residents <19 years (1 in 2287 live births) [6].

                        

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Literature review current through: Nov 2016. | This topic last updated: Fri May 15 00:00:00 GMT+00:00 2015.
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References
Top
  1. Margo CE, Hamed LM, Fang E, Dawson WW. Optic nerve aplasia. Arch Ophthalmol 1992; 110:1610.
  2. Blanco R, Salvador F, Galan A, Gil-Gibernau JJ. Aplasia of the optic nerve: report of three cases. J Pediatr Ophthalmol Strabismus 1992; 29:228.
  3. Storm RL, PeBenito R. Bilateral optic nerve aplasia associated with hydranencephaly. Ann Ophthalmol 1984; 16:988.
  4. Weiter JJ, McLean IW, Zimmerman LE. Aplasia of the optic nerve and disk. Am J Ophthalmol 1977; 83:569.
  5. Brodsky MC. Congenital optic disk anomalies. Surv Ophthalmol 1994; 39:89.
  6. Mohney BG, Young RC, Diehl N. Incidence and associated endocrine and neurologic abnormalities of optic nerve hypoplasia. JAMA Ophthalmol 2013; 131:898.
  7. Zeki SM, Dutton GN. Optic nerve hypoplasia in children. Br J Ophthalmol 1990; 74:300.
  8. Hellström A, Wiklund LM, Svensson E. The clinical and morphologic spectrum of optic nerve hypoplasia. J AAPOS 1999; 3:212.
  9. Mosier MA, Lieberman MF, Green WR, Knox DL. Hypoplasia of the optic nerve. Arch Ophthalmol 1978; 96:1437.
  10. Siatkowski RM, Sanchez JC, Andrade R, Alvarez A. The clinical, neuroradiographic, and endocrinologic profile of patients with bilateral optic nerve hypoplasia. Ophthalmology 1997; 104:493.
  11. Ahmad T, Garcia-Filion P, Borchert M, et al. Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: a prospective study. J Pediatr 2006; 148:78.
  12. Garcia ML, Ty EB, Taban M, et al. Systemic and ocular findings in 100 patients with optic nerve hypoplasia. J Child Neurol 2006; 21:949.
  13. Garcia-Filion P, Epport K, Nelson M, et al. Neuroradiographic, endocrinologic, and ophthalmic correlates of adverse developmental outcomes in children with optic nerve hypoplasia: a prospective study. Pediatrics 2008; 121:e653.
  14. Brodsky MC, Glasier CM. Optic nerve hypoplasia. Clinical significance of associated central nervous system abnormalities on magnetic resonance imaging. Arch Ophthalmol 1993; 111:66.
  15. Izenberg N, Rosenblum M, Parks JS. The endocrine spectrum of septo-optic dysplasia. Clin Pediatr (Phila) 1984; 23:632.
  16. Willnow S, Kiess W, Butenandt O, et al. Endocrine disorders in septo-optic dysplasia (De Morsier syndrome)--evaluation and follow up of 18 patients. Eur J Pediatr 1996; 155:179.
  17. Sheridan SJ, Robb RM. Optic nerve hypoplasia with diabetes insipidus. J Pediatr Ophthalmol Strabismus 1978; 15:82.
  18. Hoyt WF, Kaplan SL, Grumbach MM, Glaser JS. Septo-optic dysplasia and pituitary dwarfism. Lancet 1970; 1:893.
  19. Traggiai C, Stanhope R. Endocrinopathies associated with midline cerebral and cranial malformations. J Pediatr 2002; 140:252.
  20. Cohen RN, Cohen LE, Botero D, et al. Enhanced repression by HESX1 as a cause of hypopituitarism and septooptic dysplasia. J Clin Endocrinol Metab 2003; 88:4832.
  21. Dattani MT, Robinson IC. HESX1 and Septo-Optic Dysplasia. Rev Endocr Metab Disord 2002; 3:289.
  22. Donat JF. Septo-optic dysplasia in an infant of a diabetic mother. Arch Neurol 1981; 38:590.
  23. Strömland K, Pinazo-Durán MD. Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol Alcohol 2002; 37:2.
  24. Strömland K, Hellström A. Fetal alcohol syndrome--an ophthalmological and socioeducational prospective study. Pediatrics 1996; 97:845.
  25. McKinna AJ. Quinine induced hypoplasia of the optic nerve. Can J Ophthalmol 1966; 1:261.
  26. McMahon CL, Braddock SR. Septo-optic dysplasia as a manifestation of valproic acid embryopathy. Teratology 2001; 64:83.
  27. Hoyt CS, Billson FA. Maternal anticonvulsants and optic nerve hypoplasia. Br J Ophthalmol 1978; 62:3.
  28. Brodsky MC. Congenital anomalies of the optic disc. In: Walsh & Hoyt's Clinical Neuro-Ophthalmology, 5th ed, Miller NR, Newman NJ (Eds), Lippincott Williams & Wilkins, Philadelphia 1998. p.755.
  29. Dominguez R, Aguirre Vila-Coro A, Slopis JM, Bohan TP. Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs. Am J Dis Child 1991; 145:688.
  30. Layman PR, Anderson DR, Flynn JT. Frequent occurrence of hypoplastic optic disks in patients with aniridia. Am J Ophthalmol 1974; 77:513.
  31. Delleman JW, Oorthuys JW. Orbital cyst in addition to congenital cerebral and focal dermal malformations: a new entity? Clin Genet 1981; 19:191.
  32. Delleman JW, Oorthuys JW, Bleeker-Wagemakers EM, et al. Orbital cyst in addition to congenital cerebral and focal dermal malformations: a new entity. Clin Genet 1984; 25:470.
  33. Aguirre-Aquino BI, Rogers DG, Traboulsi EI. A patient with de Morsier and Duane syndromes. J AAPOS 2000; 4:243.
  34. Denslow GT, Sims M. Duane's retraction syndrome associated with optic nerve hypoplasia. J Pediatr Ophthalmol Strabismus 1980; 17:26.
  35. O'Connor PS, Smith JL. Optic nerve variant in the Klippel-Trenaunay-Weber syndrome. Ann Ophthalmol 1978; 10:131.
  36. Margolis S, Aleksic S, Charles N, et al. Retinal and optic nerve findings in Goldenhar-Gorlin syndrome. Ophthalmology 1984; 91:1327.
  37. Brodsky MC, Kincannon JM, Nelson-Adesokan P, Brown HH. Oculocerebral dysgenesis in the linear nevus sebaceous syndrome. Ophthalmology 1997; 104:497.
  38. Font RL, Marines HM, Cartwright J Jr, Bauserman SC. Aicardi syndrome. A clinicopathologic case report including electron microscopic observations. Ophthalmology 1991; 98:1727.
  39. Carney SH, Brodsky MC, Good WV, et al. Aicardi syndrome: more than meets the eye. Surv Ophthalmol 1993; 37:419.
  40. Teng RJ, Wang PJ, Wang TR, Shen YZ. Apert syndrome associated with septo-optic dysplasia. Pediatr Neurol 1989; 5:384.
  41. Büyükgebiz A, Erçal D, Böber E. Sotos syndrome with septo-optic dysplasia. J Pediatr Endocrinol Metab 1996; 9:497.
  42. Weichselbaum RR, Zakov ZN, Albert DM, et al. New findings in the chromosome 13 long-arm deletion syndrome and retinoblastoma. Ophthalmology 1979; 86:1191.
  43. Pe'er J, Braun JT. Ocular pathology in trisomy 18 (Edwards' syndrome). Ophthalmologica 1986; 192:176.
  44. Taban M, Cohen BH, David Rothner A, Traboulsi EI. Association of optic nerve hypoplasia with mitochondrial cytopathies. J Child Neurol 2006; 21:956.
  45. FRANCESCHETTI A, BOCK RH. Megalopapilla; a new congenital anomaly. Am J Ophthalmol 1950; 33:227.
  46. Jonas JB, Zäch FM, Gusek GC, Naumann GO. Pseudoglaucomatous physiologic large cups. Am J Ophthalmol 1989; 107:137.
  47. Maisel JM, Pearlstein CS, Adams WH, Heotis PM. Large optic disks in the Marshallese population. Am J Ophthalmol 1989; 107:145.
  48. Goldhammer Y, Smith JL. Optic nerve anomalies in basal encephalocele. Arch Ophthalmol 1975; 93:115.
  49. Young SE, Walsh FB, Knox DL. The tilted disk syndrome. Am J Ophthalmol 1976; 82:16.
  50. Brazitikos PD, Safran AB, Simona F, Zulauf M. Threshold perimetry in tilted disc syndrome. Arch Ophthalmol 1990; 108:1698.
  51. Stur M. Congenital tilted disk syndrome associated with parafoveal subretinal neovascularization. Am J Ophthalmol 1988; 105:98.
  52. Brodsky MC, Wilson RS. Retinal arteriovenous communications in the morning glory disc anomaly. Arch Ophthalmol 1995; 113:410.
  53. Pollock S. The morning glory disc anomaly: contractile movement, classification, and embryogenesis. Doc Ophthalmol 1987; 65:439.
  54. De Laey JJ, Ryckaert S, Leys A. The 'morning glory' syndrome. Ophthalmic Paediatr Genet 1985; 5:117.
  55. Haik BG, Greenstein SH, Smith ME, et al. Retinal detachment in the morning glory anomaly. Ophthalmology 1984; 91:1638.
  56. Akiyama K, Azuma N, Hida T, Uemura Y. Retinal detachment in Morning Glory syndrome. Ophthalmic Surg 1984; 15:841.
  57. Sobol WM, Bratton AR, Rivers MB, Weingeist TA. Morning glory disk syndrome associated with subretinal neovascular membrane formation. Am J Ophthalmol 1990; 110:93.
  58. Leitch RJ, Winter RM. Midline craniofacial defects and morning glory disc anomaly. A distinct clinical entity. Acta Ophthalmol Scand Suppl 1996; :16.
  59. Quah BL, Hamilton J, Blaser S, et al. Morning glory disc anomaly, midline cranial defects and abnormal carotid circulation: an association worth looking for. Pediatr Radiol 2005; 35:525.
  60. Eustis HS, Sanders MR, Zimmerman T. Morning glory syndrome in children. Association with endocrine and central nervous system anomalies. Arch Ophthalmol 1994; 112:204.
  61. Yokota A, Matsukado Y, Fuwa I, et al. Anterior basal encephalocele of the neonatal and infantile period. Neurosurgery 1986; 19:468.
  62. Auber AE, O'Hara M. Morning Glory syndrome. MR imaging. Clin Imaging 1999; 23:152.
  63. Holmström G, Taylor D. Capillary haemangiomas in association with morning glory disc anomaly. Acta Ophthalmol Scand 1998; 76:613.
  64. Komiyama M, Yasui T, Sakamoto H, et al. Basal meningoencephalocele, anomaly of optic disc and panhypopituitarism in association with moyamoya disease. Pediatr Neurosurg 2000; 33:100.
  65. Krishnan C, Roy A, Traboulsi E. Morning glory disk anomaly, choroidal coloboma, and congenital constrictive malformations of the internal carotid arteries (moyamoya disease). Ophthalmic Genet 2000; 21:21.
  66. Rieger G. [On the clinical picture of Handmann's anomaly of the optic nerve Morning glory syndrome? (author's transl)]. Klin Monbl Augenheilkd 1977; 170:697.
  67. Dureau P, Attie-Bitach T, Salomon R, et al. Renal coloboma syndrome. Ophthalmology 2001; 108:1912.
  68. Savell J, Cook JR. Optic nerve colobomas of autosomal-dominant heredity. Arch Ophthalmol 1976; 94:395.
  69. Olsen TW, Summers CG, Knobloch WH. Predicting visual acuity in children with colobomas involving the optic nerve. J Pediatr Ophthalmol Strabismus 1996; 33:47.
  70. Villalonga Gornés PA, Galan Terraza A, Gil-Gibernau JJ. Ophthalmoscopic evolution of papillary colobomatous malformations. J Pediatr Ophthalmol Strabismus 1995; 32:20.
  71. Drews RC. Heterochromia iridum with coloboma of the optic disc. Arch Ophthalmol 1973; 90:437.
  72. Theodossiadis GP, Damanakis AG, Theodossiadis PG. Coloboma of the optic disk associated with retinal vascular abnormalities. Am J Ophthalmol 1995; 120:798.
  73. Weaver RG, Cashwell LF, Lorentz W, et al. Optic nerve coloboma associated with renal disease. Am J Med Genet 1988; 29:597.
  74. Sanyanusin P, McNoe LA, Sullivan MJ, et al. Mutation of PAX2 in two siblings with renal-coloboma syndrome. Hum Mol Genet 1995; 4:2183.
  75. Sanyanusin P, Schimmenti LA, McNoe LA, et al. Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet 1995; 9:358.
  76. Ford B, Rupps R, Lirenman D, et al. Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family. Am J Med Genet 2001; 99:137.
  77. Mendelian Inheritance in Man. Papillorenal syndrome http://omim.org/entry/120330 (Accessed on August 16, 2011).
  78. Russell-Eggitt IM, Blake KD, Taylor DS, Wyse RK. The eye in the CHARGE association. Br J Ophthalmol 1990; 74:421.
  79. Pagon RA. Ocular coloboma. Surv Ophthalmol 1981; 25:223.
  80. Gündüz K, Günalp I, Erden I. Focal dermal hypoplasia (Goltz's syndrome). Ophthalmic Genet 1997; 18:143.
  81. Warburg M. Update of sporadic microphthalmos and coloboma. Non-inherited anomalies. Ophthalmic Paediatr Genet 1992; 13:111.
  82. Diven DG, Solomon AR, McNeely MC, Font RL. Nevus sebaceus associated with major ophthalmologic abnormalities. Arch Dermatol 1987; 123:383.
  83. Ascaso FJ, Del Buey MA, Huerva V, et al. Noonan's syndrome with keratoconus and optic disc coloboma. Eur J Ophthalmol 1993; 3:101.
  84. Theodossiadis GP, Kollia AK, Theodossiadis PG. Cilioretinal arteries in conjunction with a pit of the optic disc. Ophthalmologica 1992; 204:115.
  85. FERRY AP. MACULAR DETACHMENT ASSOCIATED WITH CONGENITAL PIT OF THE OPTIC NERVE HEAD. PATHOLOGIC FINDINGS IN TWO CASES SIMULATING MALIGNANT MELANOMA OF THE CHOROID. Arch Ophthalmol 1963; 70:346.
  86. Brown GC, Tasman W. Congenital Anomalies of the Optic Disc, Grune & Stratton, New York 1983. p.31.
  87. Brown GC, Shields JA, Goldberg RE. Congenital pits of the optic nerve head. II. Clinical studies in humans. Ophthalmology 1980; 87:51.
  88. Wise JB, MacLean AL, Gass JD. Contractile peripapillary staphyloma. Arch Ophthalmol 1966; 75:626.
  89. Kiratli H, Bozkurt B, Mocan C. Peripapillary staphyloma associated with orofacial capillary hemangioma. Ophthalmic Genet 2001; 22:249.
  90. Gottlieb JL, Prieto DM, Vander JF, et al. Peripapillary staphyloma. Am J Ophthalmol 1997; 124:249.
  91. Duke-Elder S. Congenital deformities. In: System of Ophthalmology, Mosby, St. Louis 1963. Vol 3, p.661.
  92. Kodama T, Hayasaka S, Setogawa T. Myelinated retinal nerve fibers: prevalence, location and effect on visual acuity. Ophthalmologica 1990; 200:77.
  93. Straatsma BR, Foos RY, Heckenlively JR, Taylor GN. Myelinated retinal nerve fibers. Am J Ophthalmol 1981; 91:25.
  94. Ellis GS Jr, Frey T, Gouterman RZ. Myelinated nerve fibers, axial myopia, and refractory amblyopia: an organic disease. J Pediatr Ophthalmol Strabismus 1987; 24:111.
  95. Ali BH, Logani S, Kozlov KL, et al. Progression of retinal nerve fiber myelination in childhood. Am J Ophthalmol 1994; 118:515.
  96. Kushner BJ. Functional amblyopia associated with abnormalities of the optic nerve. Arch Ophthalmol 1984; 102:683.
  97. De Jong PT, Bistervels B, Cosgrove J, et al. Medullated nerve fibers. A sign of multiple basal cell nevi (Gorlin's) syndrome. Arch Ophthalmol 1985; 103:1833.
  98. Lorentzen SE. Drusen of the optic disc. Dan Med Bull 1967; 14:293.
  99. Rosenberg MA, Savino PJ, Glaser JS. A clinical analysis of pseudopapilledema. I. Population, laterality, acuity, refractive error, ophthalmoscopic characteristics, and coincident disease. Arch Ophthalmol 1979; 97:65.
  100. Puck A, Tso MO, Fishman GA. Drusen of the optic nerve associated with retinitis pigmentosa. Arch Ophthalmol 1985; 103:231.
  101. Grover S, Fishman GA, Brown J Jr. Frequency of optic disc or parapapillary nerve fiber layer drusen in retinitis pigmentosa. Ophthalmology 1997; 104:295.
  102. Edwards A, Grover S, Fishman GA. Frequency of photographically apparent optic disc and parapapillary nerve fiber layer drusen in Usher syndrome. Retina 1996; 16:388.
  103. Nischal KK, Hingorani M, Bentley CR, et al. Ocular ultrasound in Alagille syndrome: a new sign. Ophthalmology 1997; 104:79.
  104. Pierro L, Brancato R, Minicucci M, Pece A. Echographic diagnosis of Drusen of the optic nerve head in patients with angioid streaks. Ophthalmologica 1994; 208:239.
  105. Beck RW, Corbett JJ, Thompson HS, Sergott RC. Decreased visual acuity from optic disc drusen. Arch Ophthalmol 1985; 103:1155.
  106. Kurz-Levin MM, Landau K. A comparison of imaging techniques for diagnosing drusen of the optic nerve head. Arch Ophthalmol 1999; 117:1045.
  107. Boldt HC, Byrne SF, DiBernardo C. Echographic evaluation of optic disc drusen. J Clin Neuroophthalmol 1991; 11:85.
  108. Merchant KY, Su D, Park SC, et al. Enhanced depth imaging optical coherence tomography of optic nerve head drusen. Ophthalmology 2013; 120:1409.
  109. Mustonen E, Nieminen H. Optic disc drusen--a photographic study. I. Autofluorescence pictures and fluorescein angiography. Acta Ophthalmol (Copenh) 1982; 60:849.
  110. Bianchi-Marzoli S, Rizzo JF 3rd, Brancato R, Lessell S. Quantitative analysis of optic disc cupping in compressive optic neuropathy. Ophthalmology 1995; 102:436.
  111. Kupersmith MJ, Krohn D. Cupping of the optic disc with compressive lesions of the anterior visual pathway. Ann Ophthalmol 1984; 16:948.
  112. Hayreh SS, Jonas JB. Optic disc morphology after arteritic anterior ischemic optic neuropathy. Ophthalmology 2001; 108:1586.
  113. Brodsky MC. Periventricular leukomalacia: an intracranial cause of pseudoglaucomatous cupping. Arch Ophthalmol 2001; 119:626.
  114. Jacobson L, Hellström A, Flodmark O. Large cups in normal-sized optic discs: a variant of optic nerve hypoplasia in children with periventricular leukomalacia. Arch Ophthalmol 1997; 115:1263.
  115. Parmley VC, Schiffman JS, Maitland CG, et al. Does neuroretinitis rule out multiple sclerosis? Arch Neurol 1987; 44:1045.
  116. Liu GT, Galetta SL, Rorke LB, et al. Gangliogliomas involving the optic chiasm. Neurology 1996; 46:1669.
  117. Stark KL, Kaufman B, Lee BC, et al. Visual recovery after a year of craniopharyngioma-related amaurosis: report of a nine-year-old child and a review of pathophysiologic mechanisms. J AAPOS 1999; 3:366.
  118. Wang YC, Huang JS, Wu CJ, et al. A huge osteoblastoma with aneurysmal bone cyst in skull base. Clin Imaging 2001; 25:247.
  119. Yee RD, Cogan DG, Thorp TR, Schut L. Optic nerve compression due to aneurysmal bone cyst. Arch Ophthalmol 1977; 95:2176.
  120. Sullivan TJ, Wright JE. Non-traumatic orbital haemorrhage. Clin Exp Ophthalmol 2000; 28:26.
  121. Kaye LC, Kaye SB, Lagnado R, et al. Cerebral arteriovenous malformation presenting as visual deterioration in a child. Dev Med Child Neurol 2000; 42:704.
  122. Ishikawa T, Ito T, Shoji E, Inukai K. Compressive optic nerve atrophy resulting from a distorted internal carotid artery. Pediatr Neurol 2000; 22:322.
  123. Neumann D, Isenberg SJ, Rosenbaum AL, et al. Ultrasonographically guided injection of corticosteroids for the treatment of retroseptal capillary hemangiomas in infants. J AAPOS 1997; 1:34.
  124. Curran EL, Fleming JC, Rice K, Wang WC. Orbital compression syndrome in sickle cell disease. Ophthalmology 1997; 104:1610.
  125. Castelnuovo P, Mauri S, Bignami M. Spontaneous compressive orbital emphysema of rhinogenic origin. Eur Arch Otorhinolaryngol 2000; 257:533.
  126. Yavuzer R, Khilnani R, Jackson IT, Audet B. A case of atypical McCune-Albright syndrome requiring optic nerve decompression. Ann Plast Surg 1999; 43:430.
  127. Birchall D, Goodall KL, Noble JL, Jackson A. Graves ophthalmopathy: intracranial fat prolapse on CT images as an indicator of optic nerve compression. Radiology 1996; 200:123.
  128. Shapiro F. Osteopetrosis. Current clinical considerations. Clin Orthop Relat Res 1993; :34.
  129. Votruba M, Fitzke FW, Holder GE, et al. Clinical features in affected individuals from 21 pedigrees with dominant optic atrophy. Arch Ophthalmol 1998; 116:351.
  130. Online Mendelian Inheritance in Man. Optic atrophy 1. http://omim.org/entry/165500 (Accessed on August 16, 2011).
  131. Fein-Levy C, Gorlick R, Meyers PA, et al. Ewing's sarcoma in a patient with congenital optic atrophy. J Pediatr Hematol Oncol 1998; 20:577.