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Frequent Occurrence of Hypoplastic Optic Disks in Patients with Aniridia
FREQUENT OCCURRENCE O F HYPOPLASTIC OPTIC DISKS IN PATIENTS WITH ANIRIDIA P A U L R. L A Y M A N , M.D.,
DOUGLAS R.
A N DERSON, M.D.,
AND J O H N T. F L Y N N ,
M.D.
Miami, Florida Hypoplasia of the optic nerve occurred in nine of 12 patients with congenital aniridia recently seen at the Bascom Palmer E y e In stitute. To our knowledge, the frequency of this association has not been previously re ported. This paper describes the nine cases of congenital aniridia that exhibited this find ing. S U B J E C T S AND METHODS
Twelve patients with aniridia were exam ined, and nine had small optic disks, repre senting hypoplasia of the optic nerve. T h e Table lists the salient features of each case, including the nystagmus, cataracts, glaucoma, corneal degeneration, and ectopia lentis that typically accompany aniridia. 1 ' 2 Of the nine patients, five were female, and four male, five were sporadic, and four familial. Eight patients had small disks in both eyes, but in Patient 4, a cloudy cornea prevented exam ination of the right fundus, and it is there fore not known whether the hypoplasia was bilateral or unilateral. Patient 9, who was the mother of Patient 4, had aniridia and bilat eral hypoplasia of the optic nerve. All patients were born after a normal nine-month gestation without complications of labor or delivery. There was no history of maternal infection or drug ingestion during pregnancy in any case. All patients appeared to have had normal growth and development except for problems relating to their visual handicap. Figures 1 and 2 show the small size of the disk, as well as the lack of foveal reflex and the lack of macular development. Figure 1 From the Bascom Palmer Eye Institute, Depart ment of Ophthalmology, University of Miami School of Medicine, Miami, Florida. Dr. Anderson holds an RPB Eye Research Professorship awarded by Research to Prevent Blindness, Inc. Reprint requests to Douglas R. Anderson, M.D., Bascom Palmer Eye Institute, P.O. Box 875, Biscayne Annex, Miami, FL 33152.
shows the extremely small (hypoplastic) disks of the most illustrative case in our series. Figure 2 represents a less striking de gree of optic nerve hypoplasia surrounded by a peripapillary halo. F o r comparison, Figure 3 shows a normal disk and macula with the same photographic enlargement from the 35-mm color transparency. DISCUSSION
Over 500 cases of aniridia and the associated findings have been extensively re corded. 1 " 3 Halbertsma 4 reported the presence of a small (hypoplastic) disk in one patient with multiple ocular anomalies including ani ridia ; in the book by Bonamour and associ ates, 5 a photograph chosen to illustrate hypo plasia of the optic nerve was of a patient who had aniridia. F r o m these isolated examples, one would assume that hypoplasia of the optic nerve was an additional anomaly that only rarely coexisted with aniridia, but our series suggests that the majority of patients with aniridia have disks that are to some extent hypoplastic. T h e reason that the frequent association has not been recognized before is probably due to the difficulty in identifying small disks on fundus examination. There are few clues to the absolute size of the disk on ophthalmoscopic examination, and magnification or minification resulting from large refractive errors compound the difficulty. However, if one looks at the vessel pattern and size in comparison to the disk size in these patients (Figs. 1 and 2) and compares it to the normal fundus (Fig. 3 ) , the disk is clearly small. None of the aniridic patients had extreme re fractive errors ( T a b l e ) , and the apparent difference in size of the disk is therefore not due to optical phenomena. T h a t the fundus photographs of the aniridia patients and the normal subjects covered approximately the
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AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL, 1974
TABLE CLINICAL FINDINGS OF NINE CASES OF ANIRIDIA WITH HYOPLASTIC DISKS Patient, Sex, Age, yr
Genetic Type
Visual Acuity
Disks
1. M, 9 mo
Sporadic
Bilateral hypoplasia
2. F, 2 3. F, 8
Sporadic Sporadic
Follows light with either eye
4. F, 10
Familial
5. M, 10
Sporadic
RE: 20/200 LE: 20/400
Bilateral hypoplasia
+
+
6. F, 13
Familial
+
Sporadic
Mild bilateral hypoplasia Bilateral hypoplasia
+
7. M, 17 8. M, 22
Familial
9. F, 28
Familial
RE: CF, 3 ft LE: CF, 2 ft RE: 20/200 LE: 2 0 / 1 0 0 RE: 20/400 LE: 20/400 RE: 20/200 LE: 20/200
RE: 20/200 LE: 20/200 RE:HM LE: CF, 6 ft
Bilateral hypoplasia Bilateral hypoplasia RE:? LE: Hypoplasia
Bilateral hypoplasia Bilateral hypoplasia
same field of view of the fundus further con firms that there is not any significant minification of the image because of abnormal refractive properties of the aniridic eye. Peripapillary halos frequently surround hy poplastic disks and may present another pit fall in diagnosis. If the peripapillary halo is erroneously viewed as disk substance, the true size of the hypoplastic disk is overesti mated (Fig. 2 ) .
Nystagmus
Cataracts
Ectopia Elevated Lends Pressure RE: ? LE: -
+ +
+ +
+ +
— -
Additional Findings Both corneas 10.5 mm; +.50 X90° bilaterally; no foveal or macular reflex +4.00 +2.00 X95° bilaterally; no foveal reflex Mother had aniridia and small disks; no foveal reflex; opaque cornea, RE R E : , + 1.00 LE: -1.00+4.00X90°; no foveal reflex Father had aniridia but not available for fundus exam RE: +1.75+.50X85° LE: +2.25 + 1.00X93° RE: -2.00 LE: -2.00 Peripapillary halos; mother of Patient 4
T h e smallness of some of the disks may not seem impressive on the photographs, but if the diameter is one half of normal, the area of the disk is only one fourth of normal, and may indicate a reduction in the number of nerve fibers that normally exit from the eye. T h e small size of the disk may be a natural consequence of poor retinal and mac ular development, apparently present in many patients with aniridia. T h e association of
Fig. 1 (Layman, Anderson, and Flynn). Left and right eyes of Patient 5, showing exceedingly small optic nerve heads.
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HYPOPLASTIC DISKS AND ANIRIDIA
515
Fig. 2 (Layman, Anderson, and Flynn). Left and right eyes of Patient 9. The disks are small and sur rounded by a ring of defective choroid and pigment epithelium. The temporal edge of the disk itself is in dicated by the arrows. aniridia and abnormal retinal development is reasonable since both the iris epithelium and musculature and the retina are derived from neuroectoderm. 1 ' 3 In the present context, in complete retinal development would result in fewer visual nerve fibers, and the optic nerve would be of small diameter. Poor retinal de velopment is evident on the fundus examina tion, since the macula is not so prominent as in normal eyes, and the foveal reflex is ab sent. 1 ' 6 Perhaps the abnormal retinal devel opment, especially at the macula, is also the reason for poor vision and nystagmus in patients with aniridia. 1 W e use the term "hypoplasia" of the optic nerve in the general sense to mean an optic nerve of reduced diameter, presumably with a reduced number of nerve fibers. Some pa tients, of course, have isolated hypoplasia of the optic nerve, 7 ' 8 without having other ocu lar anomalies such as aniridia. Since hypo plasia of the optic nerve may be the end result of any anomaly in which there are fewer than normal ganglion cells, the embryogenic mechanism in isolated optic nerve hypoplasia may or may not be the same as the embryogenic mechanism in aniridic pa tients with hypoplastic nerves. If different
embryogenic mechanisms can result in hypo plasia of the optic nerve, the clinical manifes tations could conceivably be different in terms of visual acuity, presence of nystag mus, nature of the visual field defect, and details of the configuration of the small optic disk and surrounding choroidal rings. It re-
Fig. 3 (Layman, Anderson, and Flynn). Disk and macula of a normal eye. The photographic en largement from the transparency is the same in this eye as in the other illustrations.
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AMERICAN JOURNAL OF OPHTHALMOLOGY
mains an open question whether the hypoplastic optic nerve in aniridia is the same entity (in terms of embryogenic mechanism) as isolated optic nerve hypoplasia, 9 or hypoplastic optic nerve associated with anencephaly and other grotesque central nervous system anomalies that have small optic disks and a lack of reteinal ganglion cells on histopathologic examination. 1 0 SUMMARY
Of 12 patients with congenital aniridia seen at the Bascom Palmer Eye Institute, nine had disks of small diameter, represent ing hypoplasia of the optic nerve. T h e small size of the disk is difficult to recognize, and may easily be overlooked unless specific at tention is paid to the size of the disk in rela tion to the diameter of the vessels and the vessel patterns. Since the iris pigment epithe lium and musculature is derived from the neuroectoderm, as is the retina, there might be abnormalities in retinal development asso ciated with abnormal iris development, and hypoplasia of the optic nerve may be the logical consequence of incomplete retinal de velopment (especially in the macula) with a
APRIL, 1974
reduced number of nerve fibers passing from the retina into the optic nerve. ACKNOWLEDGMENT
We are grateful to Mrs. Reva Hertes for her editorial assistance. REFERENCES
1. Duke-Elder, S.: Normal and Abnormal Devel opment. Congenital Deformities. In System of Ophthalmology, vol. 3, pt. 2. St. Louis, C. V. Mosby, 1963, p. 566. 2. Shaw, M. W., Falls, H. F., and Neel, J. V.: Congenital aniridia. Am. J. Hum. Genet. 12:389, 1960. 3. Waardenburg, P. J., Franceschetti, A., and Klein, D.: Genetics and Ophthalmology, vol. 1. Ox ford, Blackwell, 1961, p. 741. 4. Halbertsma, K. T.: Geval van een merkwaardige combinatie van aangeboren oogafwijkingen. Ned. Tijdschr. Geneeskd. 83:498S, 1939. 5. Bonamour, G., Bregeat, P., Bonnet, M., and Tuge, P.: La papille optique. Paris, Masson and Cie, 1968, p. 59. 6. Grove, J. H., Shaw, M. W., and Bourque, G.: A family study of aniridia. Arch. Ophthalmol. 74: 105, 1961. 7. Walton, D. S., and Robb, R. M.: Optic nerve hypoplasia. Arch. Ophthalmol. 84:572, 1970. 8. Edwards, W. C, and Layden, W. E.: Optic nerve hypoplasia. Am. J. Ophthalmol. 70:950, 1970. 9. Scheie, H. G., and Adler, F. H.: Aplasia of the optic nerve. Arch. Ophthalmol. 26:61, 1941. 10. Barsky, D., and Bebin, J.: Anencephaly. J. Pediatr. Ophthalmol. 4:18, 1967.
DOUGLAS R.
A N DERSON, M.D.,
AND J O H N T. F L Y N N ,
M.D.
Miami, Florida Hypoplasia of the optic nerve occurred in nine of 12 patients with congenital aniridia recently seen at the Bascom Palmer E y e In stitute. To our knowledge, the frequency of this association has not been previously re ported. This paper describes the nine cases of congenital aniridia that exhibited this find ing. S U B J E C T S AND METHODS
Twelve patients with aniridia were exam ined, and nine had small optic disks, repre senting hypoplasia of the optic nerve. T h e Table lists the salient features of each case, including the nystagmus, cataracts, glaucoma, corneal degeneration, and ectopia lentis that typically accompany aniridia. 1 ' 2 Of the nine patients, five were female, and four male, five were sporadic, and four familial. Eight patients had small disks in both eyes, but in Patient 4, a cloudy cornea prevented exam ination of the right fundus, and it is there fore not known whether the hypoplasia was bilateral or unilateral. Patient 9, who was the mother of Patient 4, had aniridia and bilat eral hypoplasia of the optic nerve. All patients were born after a normal nine-month gestation without complications of labor or delivery. There was no history of maternal infection or drug ingestion during pregnancy in any case. All patients appeared to have had normal growth and development except for problems relating to their visual handicap. Figures 1 and 2 show the small size of the disk, as well as the lack of foveal reflex and the lack of macular development. Figure 1 From the Bascom Palmer Eye Institute, Depart ment of Ophthalmology, University of Miami School of Medicine, Miami, Florida. Dr. Anderson holds an RPB Eye Research Professorship awarded by Research to Prevent Blindness, Inc. Reprint requests to Douglas R. Anderson, M.D., Bascom Palmer Eye Institute, P.O. Box 875, Biscayne Annex, Miami, FL 33152.
shows the extremely small (hypoplastic) disks of the most illustrative case in our series. Figure 2 represents a less striking de gree of optic nerve hypoplasia surrounded by a peripapillary halo. F o r comparison, Figure 3 shows a normal disk and macula with the same photographic enlargement from the 35-mm color transparency. DISCUSSION
Over 500 cases of aniridia and the associated findings have been extensively re corded. 1 " 3 Halbertsma 4 reported the presence of a small (hypoplastic) disk in one patient with multiple ocular anomalies including ani ridia ; in the book by Bonamour and associ ates, 5 a photograph chosen to illustrate hypo plasia of the optic nerve was of a patient who had aniridia. F r o m these isolated examples, one would assume that hypoplasia of the optic nerve was an additional anomaly that only rarely coexisted with aniridia, but our series suggests that the majority of patients with aniridia have disks that are to some extent hypoplastic. T h e reason that the frequent association has not been recognized before is probably due to the difficulty in identifying small disks on fundus examination. There are few clues to the absolute size of the disk on ophthalmoscopic examination, and magnification or minification resulting from large refractive errors compound the difficulty. However, if one looks at the vessel pattern and size in comparison to the disk size in these patients (Figs. 1 and 2) and compares it to the normal fundus (Fig. 3 ) , the disk is clearly small. None of the aniridic patients had extreme re fractive errors ( T a b l e ) , and the apparent difference in size of the disk is therefore not due to optical phenomena. T h a t the fundus photographs of the aniridia patients and the normal subjects covered approximately the
514
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL, 1974
TABLE CLINICAL FINDINGS OF NINE CASES OF ANIRIDIA WITH HYOPLASTIC DISKS Patient, Sex, Age, yr
Genetic Type
Visual Acuity
Disks
1. M, 9 mo
Sporadic
Bilateral hypoplasia
2. F, 2 3. F, 8
Sporadic Sporadic
Follows light with either eye
4. F, 10
Familial
5. M, 10
Sporadic
RE: 20/200 LE: 20/400
Bilateral hypoplasia
+
+
6. F, 13
Familial
+
Sporadic
Mild bilateral hypoplasia Bilateral hypoplasia
+
7. M, 17 8. M, 22
Familial
9. F, 28
Familial
RE: CF, 3 ft LE: CF, 2 ft RE: 20/200 LE: 2 0 / 1 0 0 RE: 20/400 LE: 20/400 RE: 20/200 LE: 20/200
RE: 20/200 LE: 20/200 RE:HM LE: CF, 6 ft
Bilateral hypoplasia Bilateral hypoplasia RE:? LE: Hypoplasia
Bilateral hypoplasia Bilateral hypoplasia
same field of view of the fundus further con firms that there is not any significant minification of the image because of abnormal refractive properties of the aniridic eye. Peripapillary halos frequently surround hy poplastic disks and may present another pit fall in diagnosis. If the peripapillary halo is erroneously viewed as disk substance, the true size of the hypoplastic disk is overesti mated (Fig. 2 ) .
Nystagmus
Cataracts
Ectopia Elevated Lends Pressure RE: ? LE: -
+ +
+ +
+ +
— -
Additional Findings Both corneas 10.5 mm; +.50 X90° bilaterally; no foveal or macular reflex +4.00 +2.00 X95° bilaterally; no foveal reflex Mother had aniridia and small disks; no foveal reflex; opaque cornea, RE R E : , + 1.00 LE: -1.00+4.00X90°; no foveal reflex Father had aniridia but not available for fundus exam RE: +1.75+.50X85° LE: +2.25 + 1.00X93° RE: -2.00 LE: -2.00 Peripapillary halos; mother of Patient 4
T h e smallness of some of the disks may not seem impressive on the photographs, but if the diameter is one half of normal, the area of the disk is only one fourth of normal, and may indicate a reduction in the number of nerve fibers that normally exit from the eye. T h e small size of the disk may be a natural consequence of poor retinal and mac ular development, apparently present in many patients with aniridia. T h e association of
Fig. 1 (Layman, Anderson, and Flynn). Left and right eyes of Patient 5, showing exceedingly small optic nerve heads.
VOL. 77, NO. 4
HYPOPLASTIC DISKS AND ANIRIDIA
515
Fig. 2 (Layman, Anderson, and Flynn). Left and right eyes of Patient 9. The disks are small and sur rounded by a ring of defective choroid and pigment epithelium. The temporal edge of the disk itself is in dicated by the arrows. aniridia and abnormal retinal development is reasonable since both the iris epithelium and musculature and the retina are derived from neuroectoderm. 1 ' 3 In the present context, in complete retinal development would result in fewer visual nerve fibers, and the optic nerve would be of small diameter. Poor retinal de velopment is evident on the fundus examina tion, since the macula is not so prominent as in normal eyes, and the foveal reflex is ab sent. 1 ' 6 Perhaps the abnormal retinal devel opment, especially at the macula, is also the reason for poor vision and nystagmus in patients with aniridia. 1 W e use the term "hypoplasia" of the optic nerve in the general sense to mean an optic nerve of reduced diameter, presumably with a reduced number of nerve fibers. Some pa tients, of course, have isolated hypoplasia of the optic nerve, 7 ' 8 without having other ocu lar anomalies such as aniridia. Since hypo plasia of the optic nerve may be the end result of any anomaly in which there are fewer than normal ganglion cells, the embryogenic mechanism in isolated optic nerve hypoplasia may or may not be the same as the embryogenic mechanism in aniridic pa tients with hypoplastic nerves. If different
embryogenic mechanisms can result in hypo plasia of the optic nerve, the clinical manifes tations could conceivably be different in terms of visual acuity, presence of nystag mus, nature of the visual field defect, and details of the configuration of the small optic disk and surrounding choroidal rings. It re-
Fig. 3 (Layman, Anderson, and Flynn). Disk and macula of a normal eye. The photographic en largement from the transparency is the same in this eye as in the other illustrations.
S16
AMERICAN JOURNAL OF OPHTHALMOLOGY
mains an open question whether the hypoplastic optic nerve in aniridia is the same entity (in terms of embryogenic mechanism) as isolated optic nerve hypoplasia, 9 or hypoplastic optic nerve associated with anencephaly and other grotesque central nervous system anomalies that have small optic disks and a lack of reteinal ganglion cells on histopathologic examination. 1 0 SUMMARY
Of 12 patients with congenital aniridia seen at the Bascom Palmer Eye Institute, nine had disks of small diameter, represent ing hypoplasia of the optic nerve. T h e small size of the disk is difficult to recognize, and may easily be overlooked unless specific at tention is paid to the size of the disk in rela tion to the diameter of the vessels and the vessel patterns. Since the iris pigment epithe lium and musculature is derived from the neuroectoderm, as is the retina, there might be abnormalities in retinal development asso ciated with abnormal iris development, and hypoplasia of the optic nerve may be the logical consequence of incomplete retinal de velopment (especially in the macula) with a
APRIL, 1974
reduced number of nerve fibers passing from the retina into the optic nerve. ACKNOWLEDGMENT
We are grateful to Mrs. Reva Hertes for her editorial assistance. REFERENCES
1. Duke-Elder, S.: Normal and Abnormal Devel opment. Congenital Deformities. In System of Ophthalmology, vol. 3, pt. 2. St. Louis, C. V. Mosby, 1963, p. 566. 2. Shaw, M. W., Falls, H. F., and Neel, J. V.: Congenital aniridia. Am. J. Hum. Genet. 12:389, 1960. 3. Waardenburg, P. J., Franceschetti, A., and Klein, D.: Genetics and Ophthalmology, vol. 1. Ox ford, Blackwell, 1961, p. 741. 4. Halbertsma, K. T.: Geval van een merkwaardige combinatie van aangeboren oogafwijkingen. Ned. Tijdschr. Geneeskd. 83:498S, 1939. 5. Bonamour, G., Bregeat, P., Bonnet, M., and Tuge, P.: La papille optique. Paris, Masson and Cie, 1968, p. 59. 6. Grove, J. H., Shaw, M. W., and Bourque, G.: A family study of aniridia. Arch. Ophthalmol. 74: 105, 1961. 7. Walton, D. S., and Robb, R. M.: Optic nerve hypoplasia. Arch. Ophthalmol. 84:572, 1970. 8. Edwards, W. C, and Layden, W. E.: Optic nerve hypoplasia. Am. J. Ophthalmol. 70:950, 1970. 9. Scheie, H. G., and Adler, F. H.: Aplasia of the optic nerve. Arch. Ophthalmol. 26:61, 1941. 10. Barsky, D., and Bebin, J.: Anencephaly. J. Pediatr. Ophthalmol. 4:18, 1967.