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Unilateral Hypoplasia of the Optic Nerve
UNILATERAL HYPOPLASIA OF THE OPTIC NERVE RADIOLOGIC A N D ELECTRORETINOGRAPHIC ROGER A.
EWALD, M A J .
(MC)
FINDINGS
U.S.A.
Washington, D.C. Hypoplasia of the optic nerve is found rarely as an isolated ocular abnormality in otherwise normal patients. Twelve unilateral cases 1 ' 7 have been reported in the world lit erature,* and the bilateral condition has been recorded with about equal frequency. Hypoplasia and aplasia of the optic nerve are more commonly found in association with microphthalmos and cyclopia or with such deformities as anencephaly, hydrocephalus and orbital encephalomeningocele. 3 ' 8 Most cases reported in the literature as aplasia are actually examples of partial apla sia or more specifically, hypoplasia. 9 I n true aplasia (complete absence of the optic nerve) the optic disc and central retinal ves sels are not visible on ophthalmoscopic ex amination. Bilateral cases of optic-nerve hypoplasia are usually examined and diagnosed early in life because of the marked visual incapacitation. Unilateral cases, on the other hand, may present a problem in diagnosis later in life (Case 1) or, more importantly, may be misinterpreted in children as strabismic amblyopia (Cases 2 and 3 ) . I n two previously reported cases 3 · 7 children with strabismus were followed for several years and re ceived unsuccessful occlusion therapy prior to being correctly diagnosed.
the basis of this report. Electroretinography, not previously reported in this disor der, is included in the evaluation of one of the cases. R E P O R T OF CASES CASE 1
This 18-year-old white youth was referred for administrative separation from the military service because of poor vision existing prior to induction. Vision had always been normal in the right eye and as long as he could remember the vision in his left eye was reduced to perception of light or rec ognition of hand movements in a limited field. There was no history of ocular injury or familial ocular disorders. Examination revealed a corrected visual acuity of 20/15 in the right eye and light perception with faulty projection in the left eye. The patient could appreciate hand motion in the inferior temporal field of vision. Cycloplegic re fraction was : R.E., —0.5D sph C +0.75D cyl ax. 180"; and L.E., —0.75D sph. The pupils were round and equal. The right pupil showed a normal direct light response and a very limited consensual reaction; the left pupil had a very limited direct response and a normal consensual reaction. An af ferent pupillary defect (Marcus-Gunn) was evi dent. There was a 20 prism diopter left exotropia by the Krimsky method. The globes were of equal size and external and biomicroscopic examinations revealed no abnormalities. Intraocular pressures were 12 mm Hg by applanation in both eyes and electrotonography revealed outflow facilities of 0.34 in the right eye and 0.25 in the left eye. The optic disc on the left was abnormally small, approxi mately one third normal size (fig. 1). A pigmented crescent was present on the nasal aspect of the hypoplastic disc and there was a pale peripapillary During a one-year period, three cases of cuff of granular pigmentation corresponding in size unilateral hypoplasia of the optic nerve in to a normal disc. The retinal vascular pattern was otherwise normal patients have been ob normal. The macular area was well differentiated but a foveal reflex was absent. The right disc ap served by the Ophthalmology Service, W a l peared normal and the remainder of the fundus ter Reed General Hospital. T h e clinical and was unremarkable. Dark adaptation was normal and there were no radiologic findings in these patients form abnormalities of the peripheral and central visual fields or color vision in the right eye. In the left From the Ophthalmology Service, Walter Reed eye the central visual field, utilizing the stereoGeneral Hospital. campimeter and a 18-mm test object, revealed only ♦Since preparation of this manuscript an addi a small inferior temporal island of vision. tional case of unilateral hypoplasia of the optic The wave pattern of the electroretinogram in nerve with associated disparity in optic foramina light- and dark-adapted states was normal for both size has been reported (Arch. Ophth. 76:195, eyes (fig. 2). Medical and neurologic evaluations 1966). revealed no abnormalities. Skull X-ray films were 763
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APRIL, 1967
Fig. 1 (Ewald). Hypoplasia of the left optic nerve. Case 1.
IW 16 OCk
/\ _
\ \
health. Ocular examination established that the pa tient had central fixation in the right eye and could identify two- or three-mm objects at near. The patient could not fixate with her left eye. This eye displayed searching type movements when the right eye was occluded. The right pupil showed a good direct and limited consensual reaction, while the left pupil showed a limited direct and good consensual reaction. The Marcus Gunn pupillary sign was present. With accommodation of the right eye both pupils reacted normally. Cycloplegic refrac tion was: R.E., +2.5D sph; L.E., +2.0D sph C +1.0D cyl ax 180°. External and biomicroscopy
ILW 1 6
\
V
Fig. 2 (Ewald). Electroretinogram, Case 1. Comparison of dark-adapted white (DW 16, 200V, 50 msec) to light-adapted white (LW 16, 100V, SO msec). normal and the orbits were of equal size. The left optic foramen was smaller than the right (fig. 3top). CASE 2
This three-year-old white girl was referred for evaluation of a left exotropia present for one year. The patient was adopted in infancy and a family history for ocular disorders was not available. There was no history of ocular trauma or sys temic disease and the patient was in excellent
Fig. 3 (Ewald). Smaller optic foramen (arrow) on the side of the hypoplastic optic nerve. (Top) Case 1. (Center) Case 2. (Bottom) Case 3.
HYPOPLASIA OF OPTIC NERVE
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examinations were unremarkable and a 40 prism diopter left exotropia was measured by the Krimsky method. The right fundus was unremarkable. The left nervehead was about one third normal size with a surrounding flat, grayish peripapillary cuff containing granular pigment. As in the previ ous case, the retinal vascular pattern of the left eye was normal and no foveal reflex was discerni ble. Roentgenograms of the skull and orbits were normal; the left optic foramen was smaller than the right (fig. 3-center). CASE 3
This four and one-half year-old white boy was evaluated for blindness and strabismus of the right eye noted since shortly after birth. There was no history of birth trauma or subsequent ocular in jury and the family history for ocular disease was negative. The patient was in good health with nor mal growth and development. Ocular examination revealed vision of hand mo tion in the right eye and 20/30 in the left eye. A cycloplegic refraction showed: R.E., +1.5D sph C +0.2SD cyl ax 180° ; L.E., +1.0D sph Z +0.25D cyl ax 180°. There was no direct pupillary re sponse, but a normal consensual reaction was evi dent on the right. The left pupil had a normal di rect reaction to light but no consensual response. A variable and intermittent right exotropia was present. The external and anterior segment exam inations were normal. The fundus of the left eye showed no abnormalities. The right optic disc, however, was abnormally small (one-half normal size) and similar to those in Cases 1 and 2. The retinal vasculature was normal and the foveal re flex was absent in the right eye. The right optic foramen was smaller than the left (fig. 3-bottom). Skull and orbital X-ray films were normal. COMMENT
While the disturbance responsible for the development of hypoplastic optic nerve is not completely understood,10 a plausible mechanism has been suggested by Scheie and Adler.11 About the 15 to 17-mm stage, ganglion cells begin to differentiate from the inner neuroblastic layers. The axons of these cells grow toward the optic stalk and enter the primitive epithelial papilla on their way to the brain. By the 19-mm stage the lumen of the optic stalk has been almost en tirely filled with nerve fibers. If the mesodermal elements differentiated normally, but an anomaly of differentiation in the gan glion cell layer occurred during the 17-mm stage, then a hypoplastic nervehead with normal retinal vasculature would be ex pected. Histologie evidence for this ocular
765
embryologie defect has been found in the eyes of animals and in humans when associ ated with other ocular or systemic malforma tions. 11 Whinery and Biodi6 recently reported on the correlation of the ophthalmoscopic pic ture with the microscopic examination of a human hypoplastic optic nerve. A blind eye was enucleated two days after the onset of acute angle-closure glaucoma, a time interval insufficient to produce the histopathologic changes of glaucoma. Examination revealed a scarcity of the ganglion cells and thinning of the retina, a deep excavation of the disc, atrophy of the optic nerve and absence of its sheaths. The paucity of ganglion cells in the retina was suggested as the primary de fect in hypoplasia of the optic nerve. Five cases of optic nerve hypoplasia are on file in the Registry of Ophthalmic Pa thology, Armed Forces Institute of Pathol ogy. A review of these cases revealed none in which optic-nerve hypoplasia was present as an isolated congenital anomaly. Associ ated defects included: anencephaly (three cases) ; hydrancephaly with absence of the cerebral hemispheres (one case) ; multiple ocular anomalies (one case). Consistent findings in all cases were marked paucity or absence of the ganglion-cell layer of the ret ina, absence of the nerve-fiber layer and ab sence of axis cylinders in the optic nerve. The retinal vasculature was normal. Table 1 summarizes the clinical character istic features of the three cases presented herein and previously recorded cases of uni lateral optic-nerve hypoplasia. There is no sex prediliction for this dis order and, although the unilateral cases have been nonfamilial, Kytila and Miettinen12 have observed bilateral optic nerve hypopla sia in two brothers and Missorli13 in three members of a sibship. The hypoplastic optic disc may show cupping4"6 and a pigmented crescent on the temporal aspect.2·3'6 In the case described by Walsh 4 the disc was a mottled brown-black color. A granular finely pigmented pale peri-
766
AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 1 DIAGNOSTIC FEATURES OF UNILATERAL HYPOPLASIA OF THE OPTIC NERVE
1. History of poor vision and/or strabismus since birth or1 early childhood in an otherwise normal patient -3·5-'* 2. Negative family history for ocular disease22-7 ·3,6* 3. Abnormal direct pupillary light response * 4. Insignificant refractive 1-3,6-7 error1-3,6-7* 5. Esotropia or exotropia * 6. Normal globe size and anterior segment1-7* 7. Abnormally small optic disc1-7* 8. Pale peripapillary cuff of granular pigmentation corresponding in size to a normal disc5,7* 9. Poorly differentiated macular area3 and/or ab sence of the foveal light reflex* 10. Normal retinal vasculature1-7* 11. Smaller optic foramen on the affected side2·6,7* 12. Normal electroretinogram* * Current cases
papillary cuff corresponding in size to a normal disc was observed in each of our cases and appeared to be characteristic. An other consistent finding was absence of the foveal reflex. This is unusual considering the prominent foveal light reflex normally observed in infants and young adults. This reflex has been ascribed to thickening of the perifoveal retina.14 The change in curvature of the inner retinal surface at the margin of the thickened ganglion-cell layer presumably acts as a parabolic reflector to produce the light reflex. Conceivably, an absence or marked thinning of this layer, as histologically found in optic-nerve hypoplasia, could account for this clinical finding. With the stereocampimeter an inferior temporal island of vision was plotted in the affected eye of one of the current cases (Case 1), and suggested that the crossed (nasal) fibers were less involved in the em bryologie defect than the uncrossed (tempo ral) fibers. In this regard, Missiroli13 and Schwarz15 described binasal hemianopic de fects (uncrossed fibers) in the visual fields of patients with bilateral optic-nerve hypo plasia. An important radiologie finding in each of our cases was a smaller optic foramen on the side of the hypoplastic nerve. This difference in optic foramen size was more
APRIL, 1967
marked in Cases 1 and 2 than in Case 3. Similar radiologie findings were first de scribed by Velhagen2 and subsequently by Somerville5 and Berggren.7 Cords 1 found the optic foramina to be equal. Although it is known that the diameter of the optic fo ramen may vary not only from one person to another but also between the right and left sides of the same individual,16 the cor relation noted in the cases just mentioned seems more than coincidental and indicates that the small optic foramen is an associ ated anomaly. Many controversial papers have been pub lished through the years concerning the exact origin within the retina of the por tions of the electroretinogram (ERG). The early change in electrical potential of the eye is probably due primarily to the function of the rods and cones and/or bipolar cells.17 Normal electroretinograms have been found in patients with advanced glaucoma,17'18 ju venile form of Tay-Sachs disease19 and sec ondary optic atrophy,20 conditions in which the retinal pathology is principally ganglion cell damage. Such observations have been offered as evidence that the ganglion cells do not play an essential part in the generation of the ERG. With our knowledge of the histopathologic changes in optic-nerve hypo plasia, the finding of a normal ERG in Case 1 reported herein would appear to support further the concept that the ganglion cells do not participate in the production of the ERG. Coloboma of the optic disc and optic atro phy may be considered in the differential diagnosis; however, a colobomatous disc is usually deeply cupped and two to four times larger in size than a normal disc.8 In addi tion, it is usually associated with typical colobomas of the f undus. According to Mann,10 the disc in secondary optic atrophy is of normal size but white, and the fact that the disc in aplasia (hypoplasia) is small indi cates that it was never filled with nerve fibers. Poor vision since birth and the ab sence of systemic and neurologic disease can
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HYPOPLASIA OF OPTIC NERVE
further aid in differentiating optic-nerve hypoplasia from the secondary type of optic atrophy. While little is known of congenital optic atrophy, it is considered that the nerve fibers have formed and subsequently atrophied. 8 T h e optic disc would therefore be expected to appear white and of normal size. SUMMARY
Three cases of unilateral hypoplasia of the optic nerve occurring as an isolated ocu lar abnormality in otherwise normal patients have been presented. A n associated anomaly was a smaller optic foramen on the side of the hypoplastic nerve. A n electroretinogram obtained in one case under both light- and dark-adapted conditions revealed no differ ence in the responsiveness of the retina be tween the eye with the hypoplastic optic nerve and the normal fellow eye. T h e findings in a patient of markedly re duced vision in one eye, strabismus and an abnormal direct pupillary response are sug gestive of this entity, and careful compari son of optic-disc size is recommended. A n abnormally small disc, a pale peripapillary cuff of granular pigmentation, normal reti nal vasculature, absence of the foveal reflex and a small optic foramen on X - r a y exam ination would support the diagnosis of optic-nerve hypoplasia. This congenital dis order could be misinterpreted as strabismic amblyopia and may be more common than is generally appreciated.
Walter Reed Army Medical Center (20012) ACKNOWLEDGMENT
The electroretinogram was performed by R. Hobson, Wilmer Institute, The Johns Hopkins Hos pital, Baltimore, Maryland.
767 REFERENCES
1. Cords, R. : Einseitige Kleinheit der Papille. Klin. Mbl. Augenh. 71:414, 1923. 2. Velhagen, C. : Ein Fall von einseitger Hypoplasie des Sehnerven in einem sonst normalen Au gapfel. Arch. f. Augenh. 102 :382, 1930. 3. Smith, H. E. : Aplasia of the optic nerve ; report of three cases. Am. J. Ophth. 37 :498, 1954. 4. Walsh, F. B. : Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1957, ed. 2, p. 360. 5. Somerville, F. : Uniocular aplasia of the optic nerve, Brit. J. Ophth. 46:51, 1962. 6. Whinery, R. D. and Biodi, F. C. : Hypoplasia of the optic nerve. A clinical and histopathologic correlation. Tr. Am. Acad. Ophthal. Otolaryng. 67 :733, 1963. 7. Berggren, L. : One-sided hypoplasia of the optic nerve. Acta Ophth. (Kbh.) 43:22, 1965. 8. Duke-Elder, S. : System of Ophthalmology. London, Kimpton, 1963, v. 3, pt. 2, pp. 472, 668, 683. 9. Hogan, M. J. and Zimmerman, L. E. : Ophthalmic Pathology: An Atlas and Textbook. Philadelphia, Suanders, 1962, p. 582. 10. Mann, I. : Developmental Abnormalities of the Eye. Philadelphia, Lippincott, 1957, ed. 2, p. 126. 11. Scheie, H. and Adler, F. H.: Aplasia of the optic nerve. Arch. Ophth. 26:61, 1941. 12. Kytila, J. and Miettinen, P. : On bilateral aplasia of the optic nerve. Acta Ophth. (Kbh.) 39:416, 1961. 13. Missiroli, G. : Una nuova sindrome congeni ta a carattere famigliare: ipoplasia del nervo otti co ed eniamopsia binasale. Boll. Ocul. 26:683, 1947. 14. Van Buren, J. M. : The Retinal Ganglion Cell Layer. Springfield, 111., Thomas, 1963, p. 25. 15. Schwarz, O. : Ein Fall von mangelhafter Bildung Beider Sehnerven. Arch. f. Ophth. 90:326, 1915. 16. Hartman, E. and Gilles, E. : Roentgenologic Diagnosis in Ophthalmology. Philadelphia, Lip pincott, 1959, p. 25. 17. Jacobson, J. H. : Clinical Electroretinography. Springfield, 111., Thomas, 1961, pp. 13, 149. 18. Leydhecker, G. : The electroretinogram in glaucomatous eyes. Brit. J. Ophth. 34:550, 1950. 19. Copenhaver, R. and Goodman, G. : The ERG in infantile, late infantile and juvenile amaurotic family idiocy. Arch. Ophth. €3:559, 1960. 20. Karpe, G. : The basis of clinical electroretinography. Acta Ophth. (Kbh.) Suppl. 24, 1945.
EWALD, M A J .
(MC)
FINDINGS
U.S.A.
Washington, D.C. Hypoplasia of the optic nerve is found rarely as an isolated ocular abnormality in otherwise normal patients. Twelve unilateral cases 1 ' 7 have been reported in the world lit erature,* and the bilateral condition has been recorded with about equal frequency. Hypoplasia and aplasia of the optic nerve are more commonly found in association with microphthalmos and cyclopia or with such deformities as anencephaly, hydrocephalus and orbital encephalomeningocele. 3 ' 8 Most cases reported in the literature as aplasia are actually examples of partial apla sia or more specifically, hypoplasia. 9 I n true aplasia (complete absence of the optic nerve) the optic disc and central retinal ves sels are not visible on ophthalmoscopic ex amination. Bilateral cases of optic-nerve hypoplasia are usually examined and diagnosed early in life because of the marked visual incapacitation. Unilateral cases, on the other hand, may present a problem in diagnosis later in life (Case 1) or, more importantly, may be misinterpreted in children as strabismic amblyopia (Cases 2 and 3 ) . I n two previously reported cases 3 · 7 children with strabismus were followed for several years and re ceived unsuccessful occlusion therapy prior to being correctly diagnosed.
the basis of this report. Electroretinography, not previously reported in this disor der, is included in the evaluation of one of the cases. R E P O R T OF CASES CASE 1
This 18-year-old white youth was referred for administrative separation from the military service because of poor vision existing prior to induction. Vision had always been normal in the right eye and as long as he could remember the vision in his left eye was reduced to perception of light or rec ognition of hand movements in a limited field. There was no history of ocular injury or familial ocular disorders. Examination revealed a corrected visual acuity of 20/15 in the right eye and light perception with faulty projection in the left eye. The patient could appreciate hand motion in the inferior temporal field of vision. Cycloplegic re fraction was : R.E., —0.5D sph C +0.75D cyl ax. 180"; and L.E., —0.75D sph. The pupils were round and equal. The right pupil showed a normal direct light response and a very limited consensual reaction; the left pupil had a very limited direct response and a normal consensual reaction. An af ferent pupillary defect (Marcus-Gunn) was evi dent. There was a 20 prism diopter left exotropia by the Krimsky method. The globes were of equal size and external and biomicroscopic examinations revealed no abnormalities. Intraocular pressures were 12 mm Hg by applanation in both eyes and electrotonography revealed outflow facilities of 0.34 in the right eye and 0.25 in the left eye. The optic disc on the left was abnormally small, approxi mately one third normal size (fig. 1). A pigmented crescent was present on the nasal aspect of the hypoplastic disc and there was a pale peripapillary During a one-year period, three cases of cuff of granular pigmentation corresponding in size unilateral hypoplasia of the optic nerve in to a normal disc. The retinal vascular pattern was otherwise normal patients have been ob normal. The macular area was well differentiated but a foveal reflex was absent. The right disc ap served by the Ophthalmology Service, W a l peared normal and the remainder of the fundus ter Reed General Hospital. T h e clinical and was unremarkable. Dark adaptation was normal and there were no radiologic findings in these patients form abnormalities of the peripheral and central visual fields or color vision in the right eye. In the left From the Ophthalmology Service, Walter Reed eye the central visual field, utilizing the stereoGeneral Hospital. campimeter and a 18-mm test object, revealed only ♦Since preparation of this manuscript an addi a small inferior temporal island of vision. tional case of unilateral hypoplasia of the optic The wave pattern of the electroretinogram in nerve with associated disparity in optic foramina light- and dark-adapted states was normal for both size has been reported (Arch. Ophth. 76:195, eyes (fig. 2). Medical and neurologic evaluations 1966). revealed no abnormalities. Skull X-ray films were 763
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APRIL, 1967
Fig. 1 (Ewald). Hypoplasia of the left optic nerve. Case 1.
IW 16 OCk
/\ _
\ \
health. Ocular examination established that the pa tient had central fixation in the right eye and could identify two- or three-mm objects at near. The patient could not fixate with her left eye. This eye displayed searching type movements when the right eye was occluded. The right pupil showed a good direct and limited consensual reaction, while the left pupil showed a limited direct and good consensual reaction. The Marcus Gunn pupillary sign was present. With accommodation of the right eye both pupils reacted normally. Cycloplegic refrac tion was: R.E., +2.5D sph; L.E., +2.0D sph C +1.0D cyl ax 180°. External and biomicroscopy
ILW 1 6
\
V
Fig. 2 (Ewald). Electroretinogram, Case 1. Comparison of dark-adapted white (DW 16, 200V, 50 msec) to light-adapted white (LW 16, 100V, SO msec). normal and the orbits were of equal size. The left optic foramen was smaller than the right (fig. 3top). CASE 2
This three-year-old white girl was referred for evaluation of a left exotropia present for one year. The patient was adopted in infancy and a family history for ocular disorders was not available. There was no history of ocular trauma or sys temic disease and the patient was in excellent
Fig. 3 (Ewald). Smaller optic foramen (arrow) on the side of the hypoplastic optic nerve. (Top) Case 1. (Center) Case 2. (Bottom) Case 3.
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examinations were unremarkable and a 40 prism diopter left exotropia was measured by the Krimsky method. The right fundus was unremarkable. The left nervehead was about one third normal size with a surrounding flat, grayish peripapillary cuff containing granular pigment. As in the previ ous case, the retinal vascular pattern of the left eye was normal and no foveal reflex was discerni ble. Roentgenograms of the skull and orbits were normal; the left optic foramen was smaller than the right (fig. 3-center). CASE 3
This four and one-half year-old white boy was evaluated for blindness and strabismus of the right eye noted since shortly after birth. There was no history of birth trauma or subsequent ocular in jury and the family history for ocular disease was negative. The patient was in good health with nor mal growth and development. Ocular examination revealed vision of hand mo tion in the right eye and 20/30 in the left eye. A cycloplegic refraction showed: R.E., +1.5D sph C +0.2SD cyl ax 180° ; L.E., +1.0D sph Z +0.25D cyl ax 180°. There was no direct pupillary re sponse, but a normal consensual reaction was evi dent on the right. The left pupil had a normal di rect reaction to light but no consensual response. A variable and intermittent right exotropia was present. The external and anterior segment exam inations were normal. The fundus of the left eye showed no abnormalities. The right optic disc, however, was abnormally small (one-half normal size) and similar to those in Cases 1 and 2. The retinal vasculature was normal and the foveal re flex was absent in the right eye. The right optic foramen was smaller than the left (fig. 3-bottom). Skull and orbital X-ray films were normal. COMMENT
While the disturbance responsible for the development of hypoplastic optic nerve is not completely understood,10 a plausible mechanism has been suggested by Scheie and Adler.11 About the 15 to 17-mm stage, ganglion cells begin to differentiate from the inner neuroblastic layers. The axons of these cells grow toward the optic stalk and enter the primitive epithelial papilla on their way to the brain. By the 19-mm stage the lumen of the optic stalk has been almost en tirely filled with nerve fibers. If the mesodermal elements differentiated normally, but an anomaly of differentiation in the gan glion cell layer occurred during the 17-mm stage, then a hypoplastic nervehead with normal retinal vasculature would be ex pected. Histologie evidence for this ocular
765
embryologie defect has been found in the eyes of animals and in humans when associ ated with other ocular or systemic malforma tions. 11 Whinery and Biodi6 recently reported on the correlation of the ophthalmoscopic pic ture with the microscopic examination of a human hypoplastic optic nerve. A blind eye was enucleated two days after the onset of acute angle-closure glaucoma, a time interval insufficient to produce the histopathologic changes of glaucoma. Examination revealed a scarcity of the ganglion cells and thinning of the retina, a deep excavation of the disc, atrophy of the optic nerve and absence of its sheaths. The paucity of ganglion cells in the retina was suggested as the primary de fect in hypoplasia of the optic nerve. Five cases of optic nerve hypoplasia are on file in the Registry of Ophthalmic Pa thology, Armed Forces Institute of Pathol ogy. A review of these cases revealed none in which optic-nerve hypoplasia was present as an isolated congenital anomaly. Associ ated defects included: anencephaly (three cases) ; hydrancephaly with absence of the cerebral hemispheres (one case) ; multiple ocular anomalies (one case). Consistent findings in all cases were marked paucity or absence of the ganglion-cell layer of the ret ina, absence of the nerve-fiber layer and ab sence of axis cylinders in the optic nerve. The retinal vasculature was normal. Table 1 summarizes the clinical character istic features of the three cases presented herein and previously recorded cases of uni lateral optic-nerve hypoplasia. There is no sex prediliction for this dis order and, although the unilateral cases have been nonfamilial, Kytila and Miettinen12 have observed bilateral optic nerve hypopla sia in two brothers and Missorli13 in three members of a sibship. The hypoplastic optic disc may show cupping4"6 and a pigmented crescent on the temporal aspect.2·3'6 In the case described by Walsh 4 the disc was a mottled brown-black color. A granular finely pigmented pale peri-
766
AMERICAN JOURNAL OF OPHTHALMOLOGY TABLE 1 DIAGNOSTIC FEATURES OF UNILATERAL HYPOPLASIA OF THE OPTIC NERVE
1. History of poor vision and/or strabismus since birth or1 early childhood in an otherwise normal patient -3·5-'* 2. Negative family history for ocular disease22-7 ·3,6* 3. Abnormal direct pupillary light response * 4. Insignificant refractive 1-3,6-7 error1-3,6-7* 5. Esotropia or exotropia * 6. Normal globe size and anterior segment1-7* 7. Abnormally small optic disc1-7* 8. Pale peripapillary cuff of granular pigmentation corresponding in size to a normal disc5,7* 9. Poorly differentiated macular area3 and/or ab sence of the foveal light reflex* 10. Normal retinal vasculature1-7* 11. Smaller optic foramen on the affected side2·6,7* 12. Normal electroretinogram* * Current cases
papillary cuff corresponding in size to a normal disc was observed in each of our cases and appeared to be characteristic. An other consistent finding was absence of the foveal reflex. This is unusual considering the prominent foveal light reflex normally observed in infants and young adults. This reflex has been ascribed to thickening of the perifoveal retina.14 The change in curvature of the inner retinal surface at the margin of the thickened ganglion-cell layer presumably acts as a parabolic reflector to produce the light reflex. Conceivably, an absence or marked thinning of this layer, as histologically found in optic-nerve hypoplasia, could account for this clinical finding. With the stereocampimeter an inferior temporal island of vision was plotted in the affected eye of one of the current cases (Case 1), and suggested that the crossed (nasal) fibers were less involved in the em bryologie defect than the uncrossed (tempo ral) fibers. In this regard, Missiroli13 and Schwarz15 described binasal hemianopic de fects (uncrossed fibers) in the visual fields of patients with bilateral optic-nerve hypo plasia. An important radiologie finding in each of our cases was a smaller optic foramen on the side of the hypoplastic nerve. This difference in optic foramen size was more
APRIL, 1967
marked in Cases 1 and 2 than in Case 3. Similar radiologie findings were first de scribed by Velhagen2 and subsequently by Somerville5 and Berggren.7 Cords 1 found the optic foramina to be equal. Although it is known that the diameter of the optic fo ramen may vary not only from one person to another but also between the right and left sides of the same individual,16 the cor relation noted in the cases just mentioned seems more than coincidental and indicates that the small optic foramen is an associ ated anomaly. Many controversial papers have been pub lished through the years concerning the exact origin within the retina of the por tions of the electroretinogram (ERG). The early change in electrical potential of the eye is probably due primarily to the function of the rods and cones and/or bipolar cells.17 Normal electroretinograms have been found in patients with advanced glaucoma,17'18 ju venile form of Tay-Sachs disease19 and sec ondary optic atrophy,20 conditions in which the retinal pathology is principally ganglion cell damage. Such observations have been offered as evidence that the ganglion cells do not play an essential part in the generation of the ERG. With our knowledge of the histopathologic changes in optic-nerve hypo plasia, the finding of a normal ERG in Case 1 reported herein would appear to support further the concept that the ganglion cells do not participate in the production of the ERG. Coloboma of the optic disc and optic atro phy may be considered in the differential diagnosis; however, a colobomatous disc is usually deeply cupped and two to four times larger in size than a normal disc.8 In addi tion, it is usually associated with typical colobomas of the f undus. According to Mann,10 the disc in secondary optic atrophy is of normal size but white, and the fact that the disc in aplasia (hypoplasia) is small indi cates that it was never filled with nerve fibers. Poor vision since birth and the ab sence of systemic and neurologic disease can
VOL. 63, NO. 4
HYPOPLASIA OF OPTIC NERVE
further aid in differentiating optic-nerve hypoplasia from the secondary type of optic atrophy. While little is known of congenital optic atrophy, it is considered that the nerve fibers have formed and subsequently atrophied. 8 T h e optic disc would therefore be expected to appear white and of normal size. SUMMARY
Three cases of unilateral hypoplasia of the optic nerve occurring as an isolated ocu lar abnormality in otherwise normal patients have been presented. A n associated anomaly was a smaller optic foramen on the side of the hypoplastic nerve. A n electroretinogram obtained in one case under both light- and dark-adapted conditions revealed no differ ence in the responsiveness of the retina be tween the eye with the hypoplastic optic nerve and the normal fellow eye. T h e findings in a patient of markedly re duced vision in one eye, strabismus and an abnormal direct pupillary response are sug gestive of this entity, and careful compari son of optic-disc size is recommended. A n abnormally small disc, a pale peripapillary cuff of granular pigmentation, normal reti nal vasculature, absence of the foveal reflex and a small optic foramen on X - r a y exam ination would support the diagnosis of optic-nerve hypoplasia. This congenital dis order could be misinterpreted as strabismic amblyopia and may be more common than is generally appreciated.
Walter Reed Army Medical Center (20012) ACKNOWLEDGMENT
The electroretinogram was performed by R. Hobson, Wilmer Institute, The Johns Hopkins Hos pital, Baltimore, Maryland.
767 REFERENCES
1. Cords, R. : Einseitige Kleinheit der Papille. Klin. Mbl. Augenh. 71:414, 1923. 2. Velhagen, C. : Ein Fall von einseitger Hypoplasie des Sehnerven in einem sonst normalen Au gapfel. Arch. f. Augenh. 102 :382, 1930. 3. Smith, H. E. : Aplasia of the optic nerve ; report of three cases. Am. J. Ophth. 37 :498, 1954. 4. Walsh, F. B. : Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1957, ed. 2, p. 360. 5. Somerville, F. : Uniocular aplasia of the optic nerve, Brit. J. Ophth. 46:51, 1962. 6. Whinery, R. D. and Biodi, F. C. : Hypoplasia of the optic nerve. A clinical and histopathologic correlation. Tr. Am. Acad. Ophthal. Otolaryng. 67 :733, 1963. 7. Berggren, L. : One-sided hypoplasia of the optic nerve. Acta Ophth. (Kbh.) 43:22, 1965. 8. Duke-Elder, S. : System of Ophthalmology. London, Kimpton, 1963, v. 3, pt. 2, pp. 472, 668, 683. 9. Hogan, M. J. and Zimmerman, L. E. : Ophthalmic Pathology: An Atlas and Textbook. Philadelphia, Suanders, 1962, p. 582. 10. Mann, I. : Developmental Abnormalities of the Eye. Philadelphia, Lippincott, 1957, ed. 2, p. 126. 11. Scheie, H. and Adler, F. H.: Aplasia of the optic nerve. Arch. Ophth. 26:61, 1941. 12. Kytila, J. and Miettinen, P. : On bilateral aplasia of the optic nerve. Acta Ophth. (Kbh.) 39:416, 1961. 13. Missiroli, G. : Una nuova sindrome congeni ta a carattere famigliare: ipoplasia del nervo otti co ed eniamopsia binasale. Boll. Ocul. 26:683, 1947. 14. Van Buren, J. M. : The Retinal Ganglion Cell Layer. Springfield, 111., Thomas, 1963, p. 25. 15. Schwarz, O. : Ein Fall von mangelhafter Bildung Beider Sehnerven. Arch. f. Ophth. 90:326, 1915. 16. Hartman, E. and Gilles, E. : Roentgenologic Diagnosis in Ophthalmology. Philadelphia, Lip pincott, 1959, p. 25. 17. Jacobson, J. H. : Clinical Electroretinography. Springfield, 111., Thomas, 1961, pp. 13, 149. 18. Leydhecker, G. : The electroretinogram in glaucomatous eyes. Brit. J. Ophth. 34:550, 1950. 19. Copenhaver, R. and Goodman, G. : The ERG in infantile, late infantile and juvenile amaurotic family idiocy. Arch. Ophth. €3:559, 1960. 20. Karpe, G. : The basis of clinical electroretinography. Acta Ophth. (Kbh.) Suppl. 24, 1945.