The Spectrum of Cavitary Optic Disc Anomalies in a Family M. MADISON SLUSHER, MD, R. GREY WEAVER, Jr., MD, CRAIG M. GREVEN, MD, THOMAS K. MUNDORF, MD, L. FRANK CASHWELL, MD

Abstract: The current classification of cavitary optic disc anomalies including the morphologically related entities-optic nerve pit, morning glory disc anomaly, coloboma of the optic nerve, and retinochoroidal coloboma involving the optic nerve-is inexact and confusing. Traditionally, these disc abnormalities have been regarded as distinct morphologic anomalies. Thirty-five members of a five­generation kindred with autosomal dominantly inherited optic disc anomalies were examined. Observed abnormalities in this pedigree comprised a spectrum of morphologic variants ranging from large anomalous discs to typical pits and colobomas. The findings in this family suggest a variable expression of a single autosomal dominant defect rather than the chance occurrence of three separate, distinct, but morphologically similar entities occurring in a single pedigree. Ophthalmology 96:342-347, 1989

Colobomas affecting the optic nerve and transmitted in a pedigree as an autosomal dominant defect was re­ported by Weyert1 in 1890. Savell and Cook2 studied a large family with an isolated autosomal dominant optic disc abnormality which they termed atypical coloboma. They noted a variability in the appearance of these ab­normal discs and further noted that many of these patients had serous retinal detachments and visual field defects. Babel and Farpour3 reported a family with optic nerve pits with associated macular pigmentary disturbances.

We studied a five-generation kindred with an ocular affectation confined to the optic disc. Results of exami­nation of this pedigree allowed us to document a spectrum of cavitary disc anomalies.

Originally received: November 11. 1987. Revision accepted: November 14,1988.

From the Department of Ophthalmology, Wake Forest University, Bowman Gray School of Medicine, Winston·Salem.

Presented at the American Academy of Ophthalmology Annual Meeting, Dallas, November 1987.

Reprint requests to R. Grey Weaver, Jr., MD, Department of Ophthalmology, Wake Forest University, Bowmah Gray School of Medicine, 300 S. Haw­thome Rd, Winston-Salem, NC 27103.

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MATERIALS AND METHODS

Thirty-five members of a five-generation kindred were examined (Fig 1). All patients received a complete eye examination including best-corrected visual acuity, pu­pillary examination, and a dilated fundus examination with photographs of the optic nerves and maculae. Two patients had fluorescein angiography.

Thirteen of the 15 affected individuals were screened for visual field defects on the Humphrey Field Analyzer (Program 30-2). Statistical analysis of the perimetric ex­aminations was carried out using ST A TPAC.

Visual-evoked potentials were recorded in 12 affected individuals from the CZ-OZ derivation using a Nicolet CA1000 averager, band pass 1-100 analyzing 128 or 256 responses to pattern reversal checks presented at 1.88 cy­cles per second at a distance of 1 m. Two or more trials were recorded from each eye, and abnormalities were de­clared for absolute latencies exceeding 117.4 msec for P100 wave or a right-left asymmetry of3.3 msec. Normals for our laboratory were latency 98.9 msec and interocular differences of 1.1 msec.

We defined a colobomatous disc as one that was larger than normal, having a peripapillary pigment ring, a large irregular cup, and mUltiple large cilioretinal vessel(s). Op­tic disc pits were considered to be present when there was

SLUSHER et al • CAVITARY OPTIC DISC ANOMALIES

RL RL

EBEB ~ Cavitary anomaly

• Macular disease

@ Deceased

@ Not examined

ffi Examined

o Propositus , Fig 1. Pedigree illustrating an autosomal dominant pattern of inheritance of cavitary optic disc anomalies.

a localized excavation of the disc often with a cilioretinal vessel at the margin of the excavation. Optic discs with prominent cilioretinal vessels or enlarged discs with peri­papillary pigment rings without an excavation were con­sidered anomalous.

os

RESULTS

Of 35 family members examined, 15 (10 female and 5 male patients) had optic disc abnormalities. The abnor-

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Fig 2. Patient 4. Top left, the right disc has a large temporal pit. Top right, the left colo­bomatous disc has a large central cavitary excavation with glial tissue. There is a pigment disturbance extend­ing from the left disc into the macula. Bottom, the right vi­sual field shows a superior nerve fiber bundle defect. The left visual field shows generalized depression and a superior and inferior nerve fiber bundle defect denser below.

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:::::';':::::::::::' : ..

os malities were bilateral in 13 patients. There were four patients with unilateral colobomatous optic discs. Among the fellow eyes of patients with optic nerve coloboma, three had optic nerve pits and one had an anomalous

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Fig 3. Patient 9. Top left, the right colobomatous disc shows a deep cavitary exca­vation. Top right, the left disc shows a temporal pit. Bot­tom, the right visual field shows superior and inferior nerve fiber bundle defect. The left field has an enlarged blind spot.

optic disc. The left optic disc of patient 4 (Fig 2) and right optic disc of patient 9 (Fig 3) illustrate what we considered to be colobomatous optic discs.

There were 12 patients with optic disc pits, 4 of whom

Fig 4. Patient 7. Left, the right disc has a temporal pit (white arrows). Right, the left disc has a small temporal pit (black arrows).

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SLUSHER et al • CAVITARY OPTIC DISC ANOMALIES

Fig 5. Patient 8. Leji, the right anomalous disc shows a prominent supero-temporal and infero-temporal cilioretinal vessel and a pigment ring. Right, the left disc has a large nasal pit (black arrow).

were affected bilaterally, Three patients with a unilateral optic disc pit had a colobomatous optic nerve in the fellow eye. Four patients with a unilateral optic disc pit had an anomalous optic nerve in the fellow eye. The fellow eye of the other unilateral optic disc pit patient was normal. Patient 7 (Fig 4) and patient 8 (Fig 5), illustrate what we believe are typical pits of the optic disc.

Seven patients had what we believed were anomalous optic discs. These occurred in the fellow eyes of four pa­tients with optic disc pits and one patient with a colo­bomatous disc. One patient had bilateral anomalous optic discs and one patient had an anomalous nerve with a normal fellow eye. The right disc of patient 8 (Fig 5) was considered anomalous because of the large cilioretinal vessels. Patient 10 (Fig 6) had an anomalous right optic disc and a small pit affecting the left disc.

Four patients (1, 3, 4, and 5), all of whom were 46 years of age or older, had macular pigmentary disturbances

without drusen or hemorrhage. These patients are sus­pected of having had macular detachments or schisis.4

We were able to demonstrate a macular detachment in one eye (patient 1). The late venous phase fluorescein angiogram of this eye showed no accumulation of dye in the subretinal space (Fig 7). All patients with macular changes had decreased visual acuity, ranging from 20/80 to 5/200 in the affected eye. The four patients with mac­ular changes were the only ones in whom we were able to demonstrate a delay in the PIOO wave or a nonrecord­able PIOO wave of the visual-evoked potential from the affected eye.

Thirteen of the 15 affected patients had visual field ex­aminations with the Humphrey Field Analyzer using Program 30-2. Four patients had excessive fixation losses (responded to more than 20% of stimuli presented in the blind spot) in one or both eyes. There were six examples of generalized and/or localized depression within the

Fig 6. Patient 10. Leji, the enlarged right anomalous disc shows multiple small cilioretinai vessels and a prominent peripapillary pigment ring. Right, the enlarged left disc has a small temporal pit, small temporal cilioretinal vessels, and a prominent pigment ring.

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central 30° that we believe are related to the optic disc abnormalities (Table 1).

COMMENT

The four generations of family members with an iso­lated cavitary optic disc anomaly presented herein rep­resents the largest pedigree studied to date. The fifth gen­eration could not be documented, but is inferred by the occurrence of two affected daughters in the second gen­eration, making a new mutation unlikely to be the cause of the defect in this family. Significantly, this family dem­onstrates several features considered typical of autosomal dominant defects: approximately 50% of available family members were affected, there was vertical transmission through four successive generations, and there was vari­ation in the severity of the defect when it occurred. This pedigree does not have an equal sex occurrence of the defect, although both male and female patients are af­fected.

None of the patients studied had a typical colobomatous defect affecting the retina, choroid, or iris along the region of the embryonic fissure. The optic disc abnormality in

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Fig 7. Patient 1. Top left, the right disc shows a temporal pit. The right macula is elevated without evidence of drusen or hemorrhage. The left disc shows a temporal pit. Top right, the left macula has a prominent pigment disturbance extending from the disc margin into the macula. Bottom, the late venous phase angiogram right eye shows no choroidal neovascular membrane or leakage of dye into the subretinal space.

this family, the exact mechanism of which remains un­known, must have occurred by a process other than simple nonunion of the embryonic fissure of the globe. Mann5

•6

has studied the embryonic development of the eye and found that both the optic stalk and the optic cup have a fissure. It is tempting to speculate that failure of the fissure to form posteriorly along the optic stalk would force the primitive hyaloid artery to take an anomalous course to enter the eye. One result of an unusual vascular entry into the eye could be a failure of the proper induction sequence of factors for development of the optic papilla. A spectrum of cavitary disc anomalies ranging from an anomalous disc through optic disc pits and colobomatous discs could be the clinical manifestation of this autosomal dominant genetic event.

All five patients with reduced vision had macular pig­mentary disturbances except patient 15 (a 3-year-old girl with an anomalous right disc and a left optic disc pit with a normal macula in each eye). The macular pigmentary disturbances presumably represent a prior serous macular detachment. Two of the eyes with macular pigmentary disturbances had a colobomatous optic nerve and two had an optic nerve pit. The extramacular retina in all patients in this kindred, including the four patients with

SLUSHER et al • CAVITARY OPTIC DISC ANOMALIES

Table 1. Tabulation of Findings in the Affected Family Members

Visual Acuity RAPD Field VEP Macula Disc Patient Age

Generation No. (yrs) Sex OD OS OD OS OD OS OD OS OD OS OD OS

1 67 F 10/200 5/200 NFD + D EFL NR NR A A Pit Pit 2 70 F 20/20 20/20 EFL EFL N N N AN

III 3 49 F 20/20 20/200 A EFL EFL N NR N A Pit C 4 48 F 20/20 5/200 A NFD NFD N Delay N A Pit C 5 46 M 20/20 20/80 A N PS N N N A Pit Pit 6 42 F 20/20 20/20 N N N N N N N Pit 7 34 M 20/20 20/20 N N N N N N Pit Pit 8 33 F 20/15 20/15 N N N N N N AN Pit

IV 9 28 F 20/20 20/20 NFD LBS N N N N C Pit 10 28 M 20/20 20/20 N N AN AN 11 21 M 20/20 20/20 N N N N N N AN Pit 12 18 F 20/20 20/20 NFD + LBS LBS N N N N AN Pit 13 17 M 20/20 20/20 N N N N N N Pit Pit 14 6 F 20/20 20/20 EFL D N N N N C AN

V 15 3 F 20/30 20/40 N N AN Pit

OD = right eye; OS = left eye; RAPD = relative afferent papillary defect; VEP = visual-evoked potential; A = affected; NFD = nerve fiber bundle defect; D = generalized depression; EFL = excess fixation losses; NR = nonrecordable; Pit = pit of the disc; N = normal; AN = anomalous disc; C = coloboma of the disc; PS = paracentral scotoma; LBS = large blind spot.

macular pigmentary disturbances, was normal. This is in contrast to the only other reported family with colobo­matous optic nerves reported by Savell and Cook2 in which 15 of the 30 eyes had an abnormal macula and 14 ofthe 30 eyes had abnormalities of the extramacular ret­ina. Not surprisingly, the patients reported by Savell and Cook2 had a much more profound visual loss. Thirteen of 30 eyes had a visual acuity of 20/200 or worse (5 eyes were no light perception).

Corbett et aC considered optic disc colobomas and optic disc pits to be morphologically related but separate de­velopmental effects. They suggested the term congenital cavitary anomalies of the optic disc to include both con­ditions. Our findings suggest that cavitary optic disc anomalies in this family represent a spectrum of geneti­cally determined disc anomalies which do not conform to the traditional classification of these as separate and distinct clinical entities. Moreover, in terms of this ped­igree, we observed that changes we described as "anom­alous," (i.e., peripapillary pigment rings, large irregular cups, and large cilioretinal vessels) occurred both in con­junction with cavitary defects of the disc or in the fellow eye as isolated findings. The frequency of these "anom­alous" changes suggests that they result from the same autosomal dominantly inherited defect which produced the cavitary anomaly. Within this kindred, patients with

all possible combinations of coloboma of the optic disc, optic nerve pit, anomalous optic nerve, and normal optic nerve are seen in a pattern consistent with autosomal dominant inheritance of a single genetic trait. Therefore, we conclude that these changes can be best explained as representing the variable expressivity of a single autosomal dominantly inherited defect.

REFERENCES

1. Weyert F. Zur Heriditat der opticus·Colobome. Klin Monatsbl Aguen· heilkd 1890; 28:325-31.

2. Savell J, Cook JR. Optic nerve colobomas of autosomal·dominant heredity. Arch Ophthalmol1976; 94:395-400.

3. Babel J, Farpour H. L'origine genetique des fossettes colobamateuses du nerf optique. J Genet Hum 1967; 16:187-98.

4. Lincoff H, Lopez R, Kreissig I et al. Retinoschisis associated with optic nerve pits. Arch Ophthalmal1988; 106:61-7.

5. Mann I. The Development of the Human Eye. New York: Grune & Stratton, 1969; 2:6-8.

6. Mann I. Developmental Abnormalities of the Eye, 2nd ed. Philadelphia: J. B. Lippincott Co., 1957; 116-21.

7. Corbett JJ, Savino PJ, Schatz NJ, Orr LS. Cavitary developmental defects of the optic disc: visual loss associated with optiC pit and colobomas. Arch Neuro11980; 37 :210-3.

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