Morning Glory Syndrome: Unusual Congenital Optic Disk Anomaly

MORNING GLORY SYNDROME: UNUSUAL CONGENITAL OPTIC DISK ANOMALY PETER KINDLER,

M.D.

New York, New York

From a pathogenetic point of view, con­ genital anomalies of the optic nervehead may be classified in the following way 1 : 1. Malformations of the primitive epithe­ lial papilla—In this group belong crescents, colobomata of the optic disk and, according to Badtke,2 aplasia or hypoplasia of the optic nerve and megalopapilla. 2. Excessive or deficient atrophy of the neuroglial tissue of Bergmeister's papilla— The variations of the physiologic cup of the disc and pseudopapilledema are supposed to result from this developmental defect. 3. Abnormal differentiation of pluripotential cells—Here may be listed the pits or cra­ terlike holes in the disk, which are probably produced by an abnormal differentiation of the neuroepithelium into transparent atypical retina instead of neuroglial tissue. 4. Vascular anomalies—these appear as the various forms of remnants of the hyaloid system. All of these anomalies of the optic disk are well known and cases have been reported in large numbers. They show a typical ophthalmoscopic picture and their influence on the functions of the eye has been examined. Histologie studies have elucidated their pathogenesis. In addition to these anomalies, individual patients are occasionally seen whose cases are atypical and seem unclassifiable. These un­ usual cases are rare, but are nonetheless ob­ served repeatedly in large clinics having a great number of patients ; also, they may From the Institute of Ophthalmology, Presbyte­ rian Hospital, 635 West 165th Street, New York, New York 10032. This investigation was aided by a grant from The National Foundation. This paper was presented at the Third International Conference on Congenital Malformations in the Hague (The Netherlands) on September 12, 1969. Reprint requests to Peter Kindler, M.D., Spitzwaldstrasse 157, 4123 Allschwil, Switzerland. 376

be collected in newly established groups ac­ cording to their identical appearance. I had the opportunity to observe 10 patients with a rarely seen congenital anomaly of the optic nerve which was difficult to classify. In this group, the characteristic ophthalmoscopic findings consist of a generally en­ larged area of the optic disk, definitely pink in color, funnel-shaped, excavated, and surrounded by a rather wide, gray, elevated annulus of chorioretinal pigment disturb­ ance. Streaming over this annulus, the retina appears elevated, with the retinal vessels emerging and entering the disk loop over its edge. At the bottom of the sloping nervehead is a central dot of white, fluffy tissue. The vascular pattern is often abnormal, with the vessels appearing at the edge of the disc as multiple, rather narrow branches hidden centrally by the pink and white tissue. The other parts of the eye are usually normal, particularly the peripheral retina and the fovea. The lesion occurred unilaterally in all cases. Because of its similarity to the flower, I call this anomaly the morning glory syn­ drome. The first sign which brought the patients to examination was manifested in early in­ fancy and consisted, in most cases, of strabis­ mus, or poor focusing of one eye as a result of poor vision ; this ranged between counting fingers and 20/100 in the patients whose age permitted a proper examination. These cases show a certain similarity to some of the six cases reported by Handmann 3 as hereditary central glial anomalies of the optic disk, but to my knowledge iden­ tical findings have not been reported. As I have not been able to examine any case histologically, the pathogenesis of this malfor­ mation must remain speculative for the pres­ ent. However, this description may initiate reports of corresponding findings by other

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observers and may help to clarify the nature of this lesion. CASE REPORTS The fundi were examined with the binocular in­ direct ophthalmoscope under general anesthesia. CASE 1

A three-year-old girl (fig. 1) referred by Dr. A. Donn had had an upward and outward deviation of the left eye since the age of about two years. The left disk was pink and had an irregular, white, fluffy area in its center. The disk was surrounded by a white rim and by an elevated annulus of pigment disturbance over which the retina was elevated forming a bright-light reflex. The vessels appeared as multiple branches, hidden by the central tissue. The right eye was normal in all respects. Visual acuity was 20/200 in the left eye, and color vision was not disturbed. There was a definite hypertropia of the left eye. X-ray films revealed a normal skull, sella turcica, optic canals and orbits. During the observation of two years no changes occurred. The family history is negative. CASE 2

A girl was referred by Dr. W. Kelly at the age of five weeks, an abnormality of the right eye hav­ ing been noted at birth. The right eye showed ex­ treme microphthalmos with a corneal diameter of 6.0 mm. T h e lens was clear, the ciliary body markedly distorted, and there was a retrolentai membrane with a few fine vessels. In the left eye the optic disk was surrounded by

Fig. 2 (Kindler). Drawing of left eye, Case 3. Left eye showed pink-yellow disk, surrounded by gray-black annulus. Glial strands extended over this area. an elevated pigmented annulus and the center con­ tained a fluffy, white tissue with some fine radial strands. The vascular pattern was abnormal, with multiple, rather narrow vessels appearing at the edge of the disk. There was a family history of cataracts, ,with a paternal first cousin showing congenital cataracts. CASE 3

A one-year-old girl (fig. 2) was referred by Dr. F. D. Costenbader. An esotropia of the left eye was first noted in her early infancy. Examination re­ vealed a normal right eye. The left eye showed a pink-yellow disk surrounded by a gray-black annu­ lus. Around this was an irregular area of chorioretinal depigmentation twice the size of the diameter of the disc. There were some glial strands extend­ ing over the gray annulus. A yellowish translucent area which might have b.een the result of a former hemorrhage was found at the 3 o'clock meridian. Vision was good in the right eye, while the left eye showed poor fixation. X-ray films of (he optic canals showed no abnormality. Family history showed only that two of five sib­ lings had accommodative esotropia. CASE 4

Fig. 1 (Kindler). Drawing of the left optic disk in Case 1. Disk was pink, was irregular, white, fluffy area in center, surrounded by white rim and elevated annulus of pigment disturbance.

The parents of this two-year-old boy (fig. 3) had noted a cast in his' right eye when he was a few months of age. This patient was referred to our clinic by Dr. R. C. Collins. The right fundus showed a hyperemic, somewhat edematous disk with a white center ; there was a gray elevated mass on the temporal side of the disk. Along the nasal bor­ der were some subretiiial hemorrhages. Over nine years of observation some changes have taken place in this fundus,. with the area of subretinal hemor-

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fundus showed a large optic nerve which was deeply excavated and contained a white spot on the bottom. There was an elevated annulus of dark gray pigment proliferation and around the edge of the disk some areas of fine neovascularization could be seen. An irregular area of depigmentation sur­ rounded the dark annulus. The foveal reflex was well marked. In the left fundus there was a huge, deep coloboma of the posterior pole involving the optic nerve. Skull, orbits and optic canals were radiologically normal. In the course of three years the condition in the right remained unchanged, while in the left eye a retinal detachment occurred over the area of the coloboma. Vision in the right eye was in the 20/ 200 range ; in the left eye it was counting fingers. No eye diseases in the family are known. CASE 7

Fig. 3 (Kindler). Photograph of right eye, Case 4. Fundus showed hyperemic, slightly edematous disk with white center. rhage showing pigment proliferation. Examination at the age of eight years revealed a gray, elevated annulus around the disk. At the age of 11 years, vi­ sual acuity was 20/200, the visual fields showed a slight enlargement of the blind spot, and color vi­ sion was normal. The left eye was normal at the first examination, but a peculiar, unexplained change took place over the years, with slight papilledema and fine vascular anomalies appearing in the area of the disk. Func­ tion remained normal and x-ray films of skull and optic canals showed no abnormalities. CASE S

In this four-month-old girl (fig. 4) the eye de­ fects had been noted for the first time at Babies Hospital, where she had been admitted for prema­ turity. The right eye showed a pink optic nervehead with a white, fluffy dot in the center and a sur­ rounding gray-black pigmented, elevated annulus, over which the retinal vessels looped and disap­ peared in the central tissue. The fovea was well marked. In the left eye was a typical anterior chamber cleavage syndrome, with a dense corneal opacity in the lower part and shallow anterior chamber. The iris collarette was adherent to the posterior surface of the opaque area of the cornea and the lens was cataractous, so the fundus could not be seen. Intra­ ocular pressure was normal. The conditions in both eyes remained static over one year of observation. According to the parents, the child sees well with her right eye, but there is no vision in the left eye. The family history of eye diseases is negative. CASE 6

A two-year-old girl (fig. S) had strabismus at birth. She was referred by Dr. J. Shier. The right

A one-year-old girl (fig. 6) was referred by Dr. A. G. DeVoe. An hemangioma of the right temple and the right upper and lower eyelid had been treated with dry ice. In the right fundus there was an enlarged area of the optic disk. The center contained some white tissue surrounded by a pink area. Around the nervehead was a gray, elevated annulus and some pigment proliferation. The retina showed some edema at the border of the disk. There was a gross disturbance of the vascular pattern, with about IS more or less uniform, narrow vessels coursing over the elevated edge of the disk. The fovea was nor­ mal. The left eye was normal in all respects. There was no change in this lesion during the observation of four years. When this patient was examined at the age of five years, visual acuity was 20/100 in the right eye and 20/20 in the left. There was an esotropia. There is no family history of ocular defects. CASE 8

The parents of this two-year-old boy (fig. 7) noted strabismus in his early infancy. The child was referred to our clinic by Dr. J. Boyd. The area of the left optic nerve was enlarged, showing a dark annulus of pigment proliferation and some white tissue in its center. Examination two and one-half years later revealed a retinal detachment all around the nervehead. No retinal breaks could be noted. There were some radial retinal folds, and nasal to the disk the detached retina was pigmented. In the left eye, the vision at this examination was count­ ing fingers at one or two feet; the right eye was normal with vision of 20/20. Optic canals were nor­ mal. The family history is negative. CASE 9

This 3-month-old girl, Lack, showed an abnormal a pink disk surrounded by turbance with a white dot

referred by Dr. D. C right fundus ; there was an area of pigment dis­ in the center. From the

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Figs. 4-7 (Kindler). Figure 4 (upper left) is a drawing of the right fundus in Case 5. The insert shows the appearance of the anterior chamber cleavage syndrome in the left eye. Figure 5 (upper right) shows drawing of right optic disk of Case 6. Right fundus showed large optic nerve, elevated annulus of dark gray pigment proliferation, with areas of fine neovascularization around edges of disk. Figure 6 (lower left) shows drawing of right eye in Case 7. Fundus showed enlarged area of the optic disk. There was gross disturbance of vascular pattern, with about 15 more or less uniform, narrow vessels coursing over the elevated edge of the disk. Figure 7 (lower right) Drawing of left eye in Case 8. Left optic nerve was enlarged. showing dark annulus of pigment proliferation and some wnlte tissue in Its center.

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lower edge of the cup a thin strand came forward to contact the posterior surface of the lens. There was a cyst of the ciliary body. One year later this eye showed a posterior retinal detachment with a fold over the disk. The left eye was completely nor­ mal. The optic canals were normal and symmetrical. There was no family history of eye diseases. CASE 10

This boy had had left exotropia since early in­ fancy with low vision. He was referred by Dr. T. Lewin. My examination when the child was six years of age showed a retinal detachment over the posterior pole of the left eye almost to the periph­ ery, but with the peripheral retina in place. The optic nerve was pink and had an annulus of ele­ vated gray-black pigment proliferation. The right eye was completely normal. There is no family history of eye problems. DISCUSSION

Normally, the optic nerve is developed in substance of the optic stalk. The cells of the stalk itself form only the neuroglial support­ ing tissue of the nerve, with the actual nerve fibers being the axones of the ganglion cells in the retina. The nerve sheaths and septa are derived from the surrounding mesoderm in the orbit. The fetal fissure, which extends to the distal one-third of the optic stalk, closes between the fifth and the sixth weeks (10-18 mm stage), beginning in its central part and extending to the anterior and poste­ rior end. Enclosed in the fetal fissure is the hyaloid artery which forms the fetal intra­ ocular blood system. At the place where the stalk leaves the optic cup, cells of the inner layer of the optic cup form the primitive epi­ thelial papilla. At the 10-13 mm stage, gan­ glion cells appear in the retina and their axones grow toward the primitive epithelial papilla and pass through it into the optic stalk. A little cone-shaped mass of cells of the epithelial papilla is cut off by these nerve fibers from the rest of the retina, forming the glial Bergmeister's papilla. During the fourth month of gestation these glial cells proliferate to form the sheath of the hyaloid artery. This sheath and Bergmeister's papilla atrophy with the hyaloid artery before birth, forming the physiologic excavation of the optic disk. Where the hyaloid artery passes through the disk, two small buds grow out,

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forming the main branches of the arteria centralis retinae which ramify in the nerve fiber layers and spread peripherally. Their development begins at the fourth month and is not complete until the eighth month. The pigment granules in the pigment epithelium of the retina, the outer wall of the optic cup, develop very early (5-10 mm stage). The choroid is formed by the surrounding meso­ derm, with the pigment epithelium exerting an essential influence on its proper develop­ ment. The choroid is fully developed by the seventh month. Pigment occurs here at about the fifth month. Toward the end of the sec­ ond month, the sciera begins developing, first in the anterior part of the eye, then grad­ ually extending posteriorly ; it is complete at the fifth month.4 The occurrence of symptoms of poor vi­ sual acuity in the affected eye at or soon after birth indicates the congenital nature of this anomaly. Further, the association of this condition with other congenital ocular de­ fects is suggestive of a noxious prenatal in­ fluence on the developing eye. In one case the optic nervehead of the fellow eye was colobomatous. One of the affected eyes showed remnants of the hyaloid system. One patient had a contralateral anterior chamber cleav­ age syndrome, i.e., an abnormality of the embryologie development of the anterior chamber. In one child an hemangioma of the temple and the eyelids affected the same side as the optic nerve anomaly, and in another, the fellow eye was microphthalmic. An heredi­ tary factor could not be found in any of these cases and pregnancy and delivery were generally normal. Although the clinical picture is unusual, a glioma of the optic nervehead has to be ruled out and thus, periodic examination is necessary. There were no signs of progres­ sive tumor growth in this series, the optic ca­ nals and orbits were radiologically normal in all cases and no exophthalmos has been noted. There was no evidence of von Recklinghausen's disease. Since some of the features of my findings correspond to those reported by Handmann,

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who suggested an abnormal development of glial tissue in the area of the disk, this pathogenesis must be considered. His cases showed a complete filling of the physiologic cup by a grayish tissue, whereas mine have a white dot of tissue on the bottom of a pink, deeply excavated disk. This central dot of tissue could well represent the remnant of a partially atrophied Bergmeister's papilla. Remnants of Bergmeister's papilla may ap­ pear principally in multiple forms and exten­ sions in otherwise normal eyes as the socalled membrana epipapillaris. It is seen either in connection with remnants of the hyaloid artery or without any other embryonic tissue. Only one of my patients (case 9) showed definite hyaloid remnants. In Case 3 some dense glial strands appeared on the patient's abnormal disk in place of the typical central dot. The abnormal retinal vessels, covered by the central tissue and appearing at the edge of the disk as multiple small branches, have been described by Handmann, 3 who consid­ ered them as ciliary vessels, with the central retinal vessels being absent. Although such a condition is very uncommon in man, this opinion could well explain the appearance of the vascular pattern in a number of my cases; some findings, however, suggest the presence of a central retinal vessel branching abnormally in the depths of the nervehead tissue. The connection which seems to exist ac­ cording to Mann,4 between the fate of the glial cells of Bergmeister's papilla and the development of the normal retinal blood sup­ ply is interesting. True retinal vessels never develop in those animals in which this glial tissue persists as a so-called pecten (Sauropsida). Some other observations give evidence of a disturbance of the vascular system in the area of the nervehead. In one patient (case 6) several areas of neovascularization at the edge of the disk could be seen. In another patient (case 3) a hemor­ rhage at the edge of the nervehead could be recognized; in Case 4, at the first examina­ tion the patient showed edema of the disk

MARCH, 1970

and a fresh subretinal hemorrhage at the nasal border as well as a gray area probably representing an old hemorrhage temporal to the disk. A peculiar late complication has occurred in three patients several years after the first examination. Retinal detachment is seen over the posterior pole which makes evident a cer­ tain progression of this congenital lesion. The detachment of the retina is in connec­ tion with the nervehead and varies in extent without reaching the far periphery. The ret­ ina is elevated in folds around the disk. No retinal tears have been seen and there is no evidence of any preretinal traction. Subreti­ nal exudation might well be the pathogenetic mechanism causing this type of detachment ; it is known as a secondary complication of various lesions which give rise to a vascular disturbance. Inflammatory diseases of the choroid, systemic blood and vascular dis­ eases, and choroidal and retinal tumors may cause an exudative retinal detachment.5 In lesions containing abnormal blood vessels, such as hemangiomas of the choroid and angiomas of the retina (von Hippel-Lindau disease), exudative detachment is a common complication.6·7 Schepens and Brockhurst8 reported a peculiar disease of unkown etiol­ ogy as the uveal effusion syndrome, describ­ ing it as causing a slowly progressive, often bilateral retinal detachment without retinal breaks and without any significant sign of uveitis, with spontaneous retinal «attach­ ment sometimes occurring after months or years. Associated systemic disturbances con­ sist of elevated pressure and increased pro­ tein in the cerebrospinal fluid. In my cases the time of observation is too short to give evidence of the further progression of these detachments. Whether these vascular distur­ bances represent a primary congenital anom­ aly of the blood vessels or are a secondary phenomenon, for instance resulting from some inflammatory process cannot be defi­ nitely determined at the present time. Characteristic, in this series, is the defi­ nite, ring-shaped chorioretinal pigment dis­ turbance around the nervehead. Pigment

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proliferation may often occur as a nonspe­ cific response to various stimulating pro­ cesses, causing disturbance in the blood sup­ ply or traction on the pigment-bearing tis­ sues. This also occurs in congenital defects, as at the edge of choroidal colobomata. In all but one of these cases this pigmented annulus was present at the first examination of the patient, and it did not change, so it seems to represent either a primary anomaly in the pigmented tissue around the papilla or a sec­ ondary response to some prenatal stimulus in this area. In Case 4, the patient shows an interesting development of this annulus after birth. The first observation at the age of two years revealed only a subretinal hemorrhage at the border of the disk with papilledema, and the typical gray, ring-shaped area oc­ curred later. The regularity of this annulus all around the disk is difficult to explain on a hemorrhagic or inflammatory basis.

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for a suspected glioma of the optic nerve, he found an annular mass at the edge of the pa­ pilla consisting of glial cells, fibroblasts, ves­ sels, and pigment-containing cells, probably originating from a folded, heavily gliosed retina. This anomaly was felt to be caused by an incompletely matured posterior sciera, producing a posterior displacement of the nervehead and the lamina cribrosa by the in­ traocular pressure. Unfortunately there was no report of the clinical appearance, but some features may well correspond to my findings. Although in my cases the retina ap­ peared ophthalmoscopically normal, the pres­ ence of a subretinal anular pigmented mass could be the cause of the ring-shaped eleva­ tion of the peripapillar retina. All explana­ tions concerning the mechanisms producing the unusual developmental anomaly reported here must remain pure suggestions and may be clarified only by histologie studies.

The appearance of a coloboma is differ­ ent, with the color of the sciera being en­ tirely white, as the wall of the globe consists only of abnormal retinal tissue and sciera in the colobomatous area, whereas all my cases presented a definite pink, hyperemic appear­ ance within the pigmented annulus. Colobo­ mata of the choroid, lens, ciliary body, or iris never could be demonstrated in my cases, making the diagnosis of a coloboma­ tous lesion improbable. The retinal detach­ ment occurring as a complication of cho­ roidal colobomata is the result of breaks of the retina in the colobomatous area, where the retina is not attached to its margins. 9 This is a different type of detachment, as in the anomaly described here no retinal breaks could be demonstrated. Also, the pits and craterlike holes in the optic disk which are related to colobomata have an appearance quite different from that seen in this series of patients. The former are sharply demar­ cated defects within the optic disc and are often combined with lesions of the macula.

Ten cases of an unusual congenital anom­ aly of the optic disk are reported. The nervehead is funnel-shaped, contains a dot of white tissue in its center, and is surrounded by an elevated annulus of chorioretinal pig­ ment disturbance. The retinal vessels appear as multiple narrow branches at the edge of the disk. Visual acuity is seriously dimin­ ished. The findings are compared to a simi­ lar anomaly described by Handmann who considered the central tissue as remnant of Bergmeister's papilla. Retinal detachment, which occurred as late complication in three patients in this series, is supposed to origi­ nate from exudation from anomalous retinal vessels. The pigmented annulus around the disk may be secondary to some unknown stimulus. A similar ring-shaped area consist­ ing of pigmented glial tissue was described by Pedler in an unusual coloboma of the disk. Future histologie examination may clarify the pathogenesis of this anomaly.

In 1961, Pedler" published a report of the pathology of an unusual coloboma of the optic nerve entrance. In an eye which had been enucleated from a 13-month-old child

I thank Drs. A. B. Reese and R. M. Ellsworth who made this study possible by their suggestions and advice. I also thank Dr. G. K. Smelser for his

SUMMARY

ACKNOWLEDGMENTS

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rawings kind help and encouragement. The fundus drawings are by E. G. Bethke. REFERENCES

1. Mann, I. : Developmental Abnormalitiess of the Eye. Philadelphia, Lippincott, 1957, p. 100. lien der 2. Badtke, G.: Ueber die Grössenanomalien :ksichtipapilla nervi optici, unter besonderer Berücksichti­ [bl. Augung der schwarzen Megalopapille. Klin. Mbl. genheilk. 135:502, 1959. angebo3. Handmann, M. : Erbliche, vermutlich angebo­ mit be­ berene zentrale gliöse Entartung des Sehnerveni mit in. Mbl. sonderer Beteiligung der Zentralgefässe. Klin. Augenheilk. 83:145, 1929.

4. Mann, I.: The Development of the Human Eye. New York, Grune and Stratton, 1964, p. 231. 5. Duke-Elder, S. : System of ophthalmology. St. Louis, Mosby, 1963, vol. X, p. 775. 6. Reese, A. B.: Tumors of the Eye, New York, Hoeber Med. Div., Harper & Row, 1963, p. 393. 7. Goldberg, M. F. and Duke, J. R. : Von HippelLindau disease. Am. J. Ophth. 66 :693,1968. 8. Schepens, C. L. and Brockhurst, R. J.: Uveal effusion. Arch. Ophth. 70:189, 1963. 9. Jesberg, D. O. and Schepens, C. L. : Retinal detachment associated with coloboma of the choroid. Arch. Ophth. 65:163, 1961. 10. Pedler, C : Unusual coloboma of the optic nerve entrance. Brit. J. Ophth. 45:803, 1961.

A N D T H E N A MIRACLE

The years have shown me beauty I n this world that God has made— T h e forming of each tree-bud, T h e way each root is laid, T h e flowing of the colors O n the plants, and flowers, and grass, T h e way the tall fern-fronds dip low W h e n the forest breezes pass. And God made all this beauty F o r the eye to see and know— T h e myriad shades of color, T h e whiteness of the snow. Time came the colors faded— They dimmed to lesser tint ; T h e flowers lost their brightness, T h e sunlight lost its glint. Loved faces now were indistinct— T h e smiles were not so clear,

MARCH, 1970

HAPPENED

I saw, but hazily, in fact, T h e ones that I held dear. A filmy veiling curtained The windows of my eyes, A n d only then I came to know W h a t all should realize: T h a t beauty ceases to exist W h e n shut from out our sight, That day becomes not light, nor dark 'Tis neither day nor night. But wonders happened—skilled hands held The answer to my plight, F o r lo ! a miracle was wrought—■ God gave me back my sight ! P E A R L GARRISON

70-year-old patient of John B. Dixon, M.D. Mason City,

Iowa