ocular changes in myotonic dystrophy* charlotte a

OCULAR CHANGES IN MYOTONIC DYSTROPHY*

BY Herrmann M. Burian, M.D., AND (BY INVITATION)Charlotte A. Burns, M.D.

BECAUSE LENTICULAR OPACITIES are frequently seen in myotonic dys-trophy, ophthalmologists have long been familiar with the disease.Indeed, on occasion ophthalmologists have been the first ones to makethe diagnosis, since the lenticular changes are rather typical andspecific and may occur early in the disease. In general, the myotoniccataract has been the only ocular sign, except for the ptosis of theupper lids, which ophthalmologists have associated regularly with thedisease.Of recent years more or less sporadic findings have indicated that

the ocular involvement in myotonic dystrophy is much more extensivethan had been previously reported. These findings led one to suspectthat a systematic study of the eyes of patients with myotonic dystrophywould yield information which would be not only of ophthalmologicinterest but which might also contribute to a better understanding ofthe nature of the disease.We have, therefore, taken the opportunity to make a thorough

investigation of the patients with myotonic dystrophy available to usthrough our departments of ophthalmology and neurology. To datewe have had 25 such patients. Their ages ranged from 10 to 57 years.All had well-established myotonic dystrophy. Some had been studiedpreviously by members of our Neurosensory Center.' We were inter-ested not only in the physical but also in the functional status of theeyes of these patients. In a previous report we have described ourfindings on the behavior of dark adaptation and electroretinography.2In the present paper we shall review the findings in the physicalexamination of the eyes of the same group of patients.

'From the Department of Ophthalmology and the Neurosensory Center (PaperNo. 105) of the College of Medicine of the University of Iowa. The NeurosensoryCenter is supported by Program Project Grant B-3345 from the National Instituteof Neurologic Diseases and Blindness, National Institutes of Health, Bethesda,Maryland.

TR. AM. OPHTH. Soc., vol. 64, 1966

Ocular Changes in Myotonic Dystrophy

FINDINGS

LIDS AND CONJUNCTIVA

All patients presented the well-known myotonic facies whichincluded in almost all a ptosis of one or both upper lids and a more orless pronounced enophthalmos. One patient had a definite antimongo-loid lid fissure. Eight had a seborrheic blepharitis; in three it was notrecorded. Two patients had hordeola when seen; one reported havinghad frequent hordeola in the past (Table 1).

TABLE 1. LIDS

Present Absenit Not recorded

Ptosis 21 4Blepharitis 8 14 3Hordeola 3 22

Cultures were taken from the tarsal conjunctiva of 15 patients. Ineight patients there was no growth in 48 hours on blood agar plates.From the eyes of the remaining seven patients hemolytic and non-hemolytic Staph. aureus and non-hemolytic Staph. albus were grown.

EXTRAOCULAR MUSCLES

Eleven patients had a restriction of their gaze movements in alldirections. Seven patients had a large exophoria, three an exotropia,one an esotropia with unilateral amblyopia, and one a convergenceinsufficiency. The remaining four had normal function of their extra-ocular muscles.

LACRIMAL SYSTEM

Six patients complained of epiphora: one of these had more or lessconstant epiphora; in all of them the epiphora became much worsewith cold, wind, and other irritations.The Schirmer test, considered positive if the wetting of the filter

paper was 10 mm. or less in five minutes, proved positive in 20 eyesof 13 patients and negative in 16 eyes of 11 patients. Seven patientswere not tested (Table 2).

TABLI,E 2. SCHIRMER TEST

Positive Negative Not done

Numllber of eyes 20 16 14

251

Hermann M. Burian and Charlotte A. Burns

Of the patients who complained of undue epiphora with irritation,four patients (six eyes) had a positive Schirmer test; in three patients(four eyes) the Schirmer test was negative. One patient was nottested. In seven patients in whom particular attention was paid to thisaspect, there was a pre-corneal film with oily globules and mucousstrands (Figure 1).

FIGURE 1

Cornea of right eye of a 35-year-old woman. Note the oily droplets in theprecorneal film and the old, healed ulcers near the limbus above and below.

CORNEA

Four patients showed signs of keratitis sicca. Of these, one patienthad a positive Schirmer test in both eyes; two had a positive Schirmertest in one eye; one patient was not tested.One patient had a Fuchs endothelial-epithelial dystrophy in both

eyes, one of which showed band keratopathy and exposure keratitis;one had a Fuchs delle in one eye; one had Hassel-Henle warts in one

eye; and one had a pannus in one eye. One patient had healed staphy-lococcal ulcers (Figure 1).CHAMBER ANGLE

Eighteen patients have had a gonioscopic examination; all had gradeIV open angles. Four showed whitish li'nt-like fibers on the ciliary bodyband and one had mound-like structures on the last roll of the iris.

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LENS

The lenticular changes which were seen are listed in Table 3. Onepatient was bilaterally aphakic. In 20 patients the typical iridescentmyotonic dust was seen in both lenses. The patient with aphakia hada blue crystal on the vitreous face of one eye which was in everyrespect similar to the "dust" seen in the lenses of other patients. Thefour youngest patients and one of the adults showed no iridescent dust.

TABLE 3. LENTICULAR CHANGES

PosteriorI ridescent Cortical subcapsular

dust "Snowballs" spokes plaques Aphakia

Number of eyes 40 24 3 13 2

In 12 patients (24 eyes) "snowball"-like opacities were seen. Theseincluded the four children and the one adult who had shown noiridescent dust in their lenses.

In 13 eyes of eight patients posterior subcapsular plaques werenoted; in three eyes of two patients cortical spokes were found and inthree eyes of two patients there was nuclear sclerosis. One patient hadstar-shaped remnants of the pupillary membrane on the anterior lenssurface.

INTRAOCULAR PRESSURE

The intraocular pressure, taken with the Goldmann applanationtonometer in all but three patients, was remarkably low in the 23patients (45 eyes) in whom it was checked. The average for the groupwas 10 mm.Hg; the spread was from 4 to 17 mm.Hg (Table 4 andFigure 2). When the patients were divided by age groups (Table 5),a definite decrease in intraocular pressure with advancing age becameevident.Tonography was done in 16 of the 25 patients (31 eyes). The

average C-value of these 31 eyes was .31 mm.3/min./mm.Hg with aspread from .15 to .59 mm.3/min./mm.Hg (Table 4 and Figure 3). Abreakdown by age groups showed no significant differences (Table 6).

FrUNDIWe were especially intercsted in a careful study of the ocular fundi

of the patients. In all of them the optic disc appeared to be normal inshape, outline, and color, although several showed a greenish-brownhalo around the disc.

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TABLE 4. INTRAOCULAR PRESSURE AND C-VALUES

Intraocularpressure C-values

Name Sex Age G. D. O.S. G. D. O.S.

PH F 10 13 17 .37 .36JY F 13 14 16IS F 15 10 1(IM F 28 15 15 .22 .30RB F 32 13 11 .38 .25*RW M 33 12.2 12.3 - -LP F 35 9 5 .42 .39HdeJ F 36 12 13 .31 .34MJ M 36 9 9 .36 .36GH M 37 6 4 > 39 > 30DH F 37 8 8 .53 .42JM M 37 10 11 .30 .29JR M 38 6 5 > 28 > 15LC F 38 <10 <10 -DMcK M 41 10 .29WW M 41 10 10 .32 .45PR M 50 6 8 .32 .45*ED M 50 10.2 10.7 .39 .32LK F 51 10 10 -

*SJ M 52 7.1 7.1 .51 .59LH F 53 7 7 .42 .39RG M 57 10 10 -JG M 38 10 10) -

Average of I.O.P. of 23 patients (43 eyes): 10 mm.HgAverage of C-value of 16 patients (31 eyes): 36 mm.3/min./mm.Hg*Measured with Schiotz tonometer. All others by applanation.

TABLE 5. AVERAGE INTRAOCULARPRESSURE BY AGE GROUPS

Number ofAge patients I .O. P.

10-15 3 13.328-36 6 11.237-41 7 8.350-57 6 8.5

TABLE 6. AVERAGE C-VALUES BY AGE GROUPS

Number ofAge patients C-value

10 1 .3628-36 5 .3337-41 6 (11 eyes) .3450-53 4 .40

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E155

<5 5-8 9-12 13-16 >16mmHg

FIGURE 2

Histogram of intraocular pressure.

In 14 of the patients no anomalies of the posterior pole of the eyeswere seen; in six the macular areas were definitely abnormal and inthe remaining five they were questionably abnormal. When macularchanges had occurred, the retina at the posterior pole had a peculiarlyhazy and almost puckered appearance. This haze was not due to cloud-ing of the media. It was responsible for a certain lack of definition inthe fundus photographs reproduced here.The fully developed macular anomalies in these patients had rather

characteristic features (Figure 4). There was a pigment disturbancewhich took the form of a streak, radiating more or less from the fovea.In some patients there was only one such streak; in others there werethree to five, giving somewhat of a stellate configuration.

22 5

Her56Hrann Al. Buriati atd Charlotte A. Burns

S1o

<21 21-30 31-40 41-50 >50mm3/min /mm HgFIGURE :3

Histogralm of C-vaclutes;.

Comparison of the macular lesions in the eyes of different patients(Figures 5, 6, and 7) gave certain hints about the possible genesis ofthese pigment streaks. There seemed at first to be whitish lesions, onoccasion appearing diffuse in shape (Figure 5) but generally streak-like (Figure 7), located deep in the retina or behind it (Bruch'smembrane ?). Above these one noted pigment spots of varying sizeswhich coalesced to make a streak-like arralngement of the pigmentwhen the process had advanced further.Four patients had clumpy peripheral retinal pigmentation, seen in

indirect ophthalmoscopy (Figure 8); nine others showred no suchpigmentation. Twelve patients were not examined with the indirectophthalmoscope but direct ophthalmoscopy did not reveal peripheralpigmentation. One of the four patients had also a macular disturbance;the other three did not.

Unusually narrow arterioles wTere noted in 14 patients (Figure 9);this narrowving wzas particullarly pronounced in four of them.Fundus photography after intravenous flulorescein injection wvas done

in six patients. It added no new informaltion.

2d56

Ocuclar Changes in Alyotonic Dystrophy

FIGURE 4Posterior pole of fundus of left eye of a 50-year-old mnan. Notethe streak-like arrangemient of the pigment clumilps radiating fromthe fovea, as well as the wlhite streak going fronm the macula to

the disc.

VISUAL ACUITY

The majority (35) of the 50 eyes had a vision of 20/15 to 20/30(Table 7). In most of the eyes in which the vision was lower than20/30 the reduction in acuity could be attributed to either lenticular,macuilar, or other changes. Only in three eyes (one with a vision of20/100, two with a vision of 20/70) was there no obvious reason forthe reduced visual acuity.

COLOR VISION

Sixteen patients had normal color vision as tested by the AOHRRcolor plates and/or the Farnsworth Dichotomous Test. Eight patientsvere not tested and one male patient had a deutan defect.

2J57

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F;4.

0

ocd

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>oci E iCZ

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_40

rY X

o C'

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FIGURE 7

Posterior pole of fundus of left eye of a 36-year-old man. Note pigmented areanasal to macula and branching white streaks temporal to it.

VISUAL FIELDS

Visual fields were obtained with the Goldmann perimeter in 22 ofthe 25 patients. Isopters were determined with the X mm.2 white testobject at relative intensities .096 and 1.00 and with the white 64 mm.2test object at relative intensity 1.00. Twelve of the 22 patients hadnormal isopters; one showed a slight concentric constriction; one hada (probably artifactual) altitudinal hemianopia; seven had a markedconcentric constriction of all isopters. Four patients had a baring ofthe blind spot.

ERG AND DARK ADAPTATIONThe behavior of these two functions, reported in detail in a previous

paper,2 will be briefly summarized.The ERG in patients with myotonic dystrophy was found to be of

remarkably low voltage owing primarily to a low amplitude of theb-wave. The average amplitude of the b-wave, measured from thetrough of the a-wave to the peak of the b-wave, for the dark-adapted

259


FIGURE 8

Periphery of fundus of left eye of a 52-year-old man (same eyeas shown in Figtire 5). Note gross, clumpy pigmentation.

eyes of the whole group, elicited with a white light of maximum inten-sity, was 200 microvolts as compared to an average of 440 microvoltsin a group of normal subjects (Figure 10). The a-wave was of relativelynormal size. The average amplitude of the a-wave was 120 microvoltsin the myotonic patients as compared to an average of 150 microvoltsin the group of normal subjects. The severe ERG changes pointed toconsiderable retinal damage and were the more striking in the patientswho had perfectly normal appearing fundi.The binocular dark-adaptation curves, obtained on the Goldmann-

Weekers adaptometer, were not in keeping with the ERG abnormality.The curves had a biphasic character and presented on the whole onlya minor elevation of the thresholds, amounting to 0.6 to 0.8 log units.However, when the patients were tested with smaller (2-degree) cen-trally fixated objects, and when perimetric absolute thresholds were

260n


FIGURE 9

Posterior pole of fundus of left eye of a 53-year-old woman. Note narrownessof arterioles.

TABLE 7. VISUAL ACUITY

Visual Numberacuity of eyes Remarks

20/15 220/20 1420/30 1920/40 2 Both eyes showed peripheral pig-

menitation of retinas.20/50 5 All eyes had posterior subcapsular

plaques.20/70 5 1 eye showed macular changes; 2

eyes had corneal disease and pos-terior subcapsular plaques; 2 eyeshad no obvious reasoni for lowvision.

20/100 1 No obvious reason for low visiondetermined.

<20/100 2 1 eye had amblyopia with estotropia;1 eye had sustained perforatingi_injury.

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determined, a considerable functional deficit was found, especiallywith blue test objects. These findings left no doubt about the impair-ment of the retinal sensitivity, particularly of the rod system.

700-

c 600-OEl Myotonic DystrophyR Patients

500 * Normal ControlB1 Subjects

400 Bred blue

300

ZZ I2AI

A1100- 2 |l

I3.3 2.7 2.5 2.0 1.5 1.3 1.0 0.5 0.1 0.0 116 I I4

FILTER DENSITYFIGURE 10

Average amplitudes of a- and b-waves of 48 eyes of patients with myotonicdystrophy (open circles) and of 24 eyes of control subjects (full circles).

Curves based on data published in paper by Burian and Burns.2

DISCUSSION

It is evident from the findings related in this paper that the eyeparticipates to a much larger extent in the disease process of myotonicdystrophy than is generally recognized. We shall now discuss thesefindings in the light of the pertinent literature without attempting acomplete survey.The ptosis of the upper lids and the frequent involvement of the

extraocular muscles form an almost constant part of the clinical pictureof myotonic dystrophy. Histologic studies of levator muscles obtainedby autopsy (Wohlfart,3 Davidson4) or from ptosis repair operations(Pendefunda, et al.5), and of extraocular muscles obtained at autopsy(Davidson4), have given evidence of dystrophic alterations.

Blepharitis is also often noted as occurring in patients with myotonic

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dystrophy. It is interesting that in two patients described by Allen andBarer6 blepharitis was actually the reason why they presented them-selves for an ophthalmic consultation. After a presumptive diagnosisof myotonic dystrophy was made, they admitted to muscular weaknessand myotonic difficulties of their grasp (one of them "reluctantly").The findings regarding the lacrimal apparatus are especially sig-

nificant. Epiphora is encountered rather frequently in the disease. Sixof our patients complained of it. However, the Schirmer test waspositive in 20 out of 36 eyes in which the test was done (Table 2). Itwas even positive in six eyes of four of the patients who complainedof excessive lacrimation with irritation of the eyes by cold or wind.

So far as we could see from the literature, aside from ourselves, onlyPendefunda and coworkers5 have performed Schirmer tests in myotonicpatients. They obtained no pathologic values in any of their 30 patients.Since these authors did not state what they considered to be abnormalvalues, it is difficult to evaluate their result. In histologic sections oflacrimal glands the same authors have found infiltrations with roundcells. The results obtained by us in the Schirmer test leave little doubtthat the lacrimal secretion is abnormally low in a large number ofmyotonic patients. This finding may have some significance for theinterpretation of the disease itself, as will be discussed below, and isvery likely to have some clinical significance with regard to the cornealabnormalities which we have observed.The number of patients with keratitis sicca was remarkably high

(4 out of 25). Other trophic abnormalities of the cornea were alsoseen. These changes may be related to the lack of lacrimal secretionor have an independent neurotrophic etiology. Corneal changes arevery rarely mentioned in the literature on myotonic dystrophy. How-ever, as early as 1926 Maillard reported a case of myotonic dystrophywith degenerative corneal changes aggravated in one eye by lensextraction. Pendefunda and coworkers5 have more recently reported ona variety of corneal dystrophic changes. We did not test the cornealsensitivity systematically in our patients, but reduced corneal sensi-tivity has been reported in myotonic dystrophy (Maillard,7 Verrey,jPendefunda, et al.5 ). We are not prepared to say whether the reducedcorneal sensitivity is a primary or secondary phenomenon in myotonicpatients.The lenticular changes in their various forms which we saw were

typical and characteristic of myotonic dystrophy. It should be pointedout that lenticular changes were found in every patient. We side,

263


therefore, with those, such as Vos,9 who believe that lenticular changesare a constant phenomenon in myotonic dystrophy, in contrast toKuhn and Piesbergen.10The behavior of the intraocular pressure represents another fasci-

nating aspect of the ocular anomalies in myotonic patients. Low intra-ocular pressure readings in an occasional patient were recorded inyears past, but the first systemic study was made by Brand." Thisworker found in 12 patients an intraocular pressure ranging from 9 to19 mm.Hg, with four eyes measuring 9 to 10 mm.Hg, 13 eyes measuring11 to 13 mm.Hg, and seven eyes measuring 14 to 19 mm.Hg. Similarfindings were reported by Kuhn and Piesbergen'0 who noted in 13patients pressures ranging from 8 to 18 mm.Hg. Pendefunda andcoworkers5 also noted ocular hypotony in their patients, giving a spreadof measurements from 8 to 15 mm.Hg.The range of our intraocular pressure readings (4 to 17 mm.Hg,

Table 4) was lower than that of these authors. This may be becausewe measured the pressure by applanation, whereas the other workersemployed the Schiotz tonometer. It is also of interest that in ourmaterial there was a decrease of the intraocular pressure with age(Table 5). Presumably this corresponded to the general progress ofthe disease.Brand" claimed that hypotony occurred only in eyes with myotonic

cataracts. Kuhn and Piesbergen'0 stated that the two could occurindependently of one another. We have found lenticular opacities(when do they become a "cataract"?) in all our patients. It is quitepossible that both the lenticular opacities and the low intraocularpressure derive from the same pathologic process. Vos9 has expressedthe attractive thought that they are both based on an atrophy of theciliary body. Thus far, there is no evidence for this assumption savethe one case studied anatomically and mentioned by Vos.9 The problemis of considerable interest and we have at present a study under wayin an attempt to determine in some detail the fluid dynamics and theorigin of the low pressure of the eyes of myotonic patients.Brand" takes the view that the ocular hypotony is caused by a

disturbance of the centers in the hypothalmus regulating the intra-ocular pressure. He accepts the theory according to which myotonicdystrophy results from pluriglandular endocrine insufficiency (Verrey8 )which is in turn due to anomalies in the function of the vegatativecenters in the hypothalmus (Curschmann12). We might add here thatThompson and coworkers' also favored a midbrain lesion as an explana-tion of the pupillary anomalies which they discovered.

264


Particularc eImphasis is placled by Brand'1 on the role of the gonadson the intraocuilar pressuire in patients witlh myotonic dystrophy. Hepoints to the lowv intraocuflar presstire in euintuchs and to the atrophyof the testes freqIuently seen in myotonic dystrophy. He reports thatin one patient in whom the testicular atrophy was greater on one sidethan on the other, the intraocular pressure was lower by 2-3 mm. inthe contralateral eye, an observation which he relates to the one madeby Kambara in a patient with testicular chorionepithelic*ma13 and tothe experimental work of Radnot with unilateral castrations inanimals.14 To what extent the abnormalities of the gonads and otherendocrine glands are responsible for the alterations in the intraocularpressture remains an open question. Many years ago Fleischer' 5 pointedout that their coexistence with lenticular changes does not force oneto accept them as the cause of the latter.Of central interest to us was the examination of the ocular fundi.

Lbhlein1" and Heine"" (cases 6 and 9) have described optic nerveatrophies.* Franceschetti and coworkers1'! stated that in patients withmyotonic dystrophy there is in general a temporal pallor of the disc.We have not been able to confirm this in our material in which wesaw neither optic nerve atrophy nor temporal pallor of the disc.We did, however, find in six patients definite macular changes and in

five the appearance of the macula was not entirely normal but couldnot be described as being definitely abnormal. It is important to notethat the instances of macular anomalies in myotonic dystrophyrecorded in the literature were either sporadic cases, or cases belong-ing to the same sibship. W\e saw macular changes in members ofunrelated sibships which would indicate that the occurrence of retinalchanges in myotonic dystrophy is not a coincidence, as was thoughtby WValsh"' and also by Davidson,4 but is part of the disease process.The morphology of the macular changes observed by us was rather

characteristic. The first description of macular changes in the literature,by Verwey and Legras,' stated that the macula of the right eye dis-played a degeneration with star-like pigmentation, such that pigmentedlines appeared which spread out in the shape of a five-pointed star.This corresponds to the changes which we have seen. Other descrip-tions of macular degenerations differ from our observations. In themacula of the left eye of the patient of Verwey and Legras2' there was

*Hauptmannl7 is quoted by Davidson4 and by Franceschetti and coworkers19as having reported an optic nerve atrophy in his patient. He states, however,specificallyl7a that the eyegrounds were normal. His seconcl paperl7b is a theo-retical one without a case report.

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a fine yellow spot. Verrey8 saw in a 39-year-old female patient, witha vision of 0.8 in the right and 1.0 in the left eye, a small dark, almostcircular spot with unsharp margins nasally above the fovea, sym-metrically placed in each eye; the maculas showed fine yellowish andslate-colored spots. Wohlfart3 mentions that in the patient who cameto autopsy (Case 1) there were collections of pigment and remnantsof a central retinochoroiditis. This may or may not agree with thepicture in our cases. No histopathologic studies of the eyes werereported. Four members of a family with myotonic dystrophy seen byBegaux and Decock22 presented macular regions of brick red appear-ance surrounded by pronounced yellowish reflex lines. Magistretti23whose descriptions we report after Franceschetti and coworkers19 sawthree myotonic patients with macular degeneration; in the first shesaw in the macular area of each eye a shiny light yellow plaque,divided, especially in its center, by yellow lines into numerous smallmore or less rectangular plaques, reminiscent of the drusen of Bruch'smembrane seen in Doyne's honeycomb choroiditis. This picture hassome similarity with the one presented by our patients reproduced inFigure 5. The sister of Magistretti's patient also had bilateral maculardegenerations, but these were more of the ordinary senile type. Herthird, unrelated patient had small, glistening yellowish spots in theparamacular region. Slatt25 mentions four cases of macular and para-macular degeneration in 17 cases studied describing "greyish-whitestippling." Lastly, Adriaenssen24 has described a macular degenerationof the Stargardt type in a 35-year-old myotonic patient whose twobrothers, also affected by myotonic dystrophy, had normal fundi.

Peripheral retinal pigmentation in myotonic dystrophy has also beendescribed in the literature, but to our knowledge only in threeinstances. Godtfredsen26 has seen a patient who complained of severenight blindness since childhood who had waxy discs, narrow arterioles,and in the retinal periphery perivascularly arranged pigment clumps ofdifferent shapes and sizes but none of the typical bone corpuscleshape. The visual fields were constricted. A case of retinitis pigmentosaassociated with myotonic dystrophy was also mentioned by Iger-sheimer27 and an additional one was reported by Bajaj.28 We did nothave an opportunity to read his original description. In our materialthere were four patients who showed gross clumpy peripheral retinalpigmentation. However, the pigment was not arranged perivascularlyand in no way resembed the pigment seen in retinitis pigmentosa(Figure 8).In spite of the relative youth of our patients, narrowing of the

266

Ocular Changes in Myotonic Dystrophy 267

arterioles was seenl in more than one-lhalf of them. HeinelS also men-tions narrowt arteries in his case 6, a 36-year-old man.

It is surprising how few descriptions of the fundi of myotonicpatients are found in the older literature. The description of the eyefindings almost always stopped at the lens, even if the lentictlarchanges were so minor as to allow a clear view of the interior of theeye. The implication is that no abnormalities were seen. Our experi-ence-reinforced by the more recent literature-makes Us believe thatanomalies of the retinas regularly accompany the other anomalies ofmyotonic dystrophy. This belief has become a certainty through ourfuinctional stuidies of the retinas.

Already in 1959 Vosl'had suggested that studies of color vision, darkadaptation, electroretinography, and biochemistry might settle theqluestion of a possible abiotrophic involvement of the eye in myotonicdystrophy. Unaware of this suggestion we have found a markeddepression of the ERG and a definite functional deficit of dark adapta-tion, regardless of whether or not there vere ophthalmoscopiciallyvisible changes in the fundi, and even in children whose retinasappeared perfectly healtlhy. Clearly, then, functional changes-presentin all patients seen by us-precede, often for a long time, anatomicchanges in the retina.One of the reasons why fundus changes might not have been sus-

pected in myotonic dystrophy is the relatively good visual acuity ofthese patients, except where there are advanced cataractous lensopacities. This relatively good vision was also found in our patients(Table 7). Very few reports in the literature are concerned with thevisual field of myotonic patients. The 29-year-old female patientdescribed by Lhlein'lhad an acuity of 0.4 in the right eye; the lefteye saw after cataract extraction 0.2 with +12.00 sph. The discs wereyellowish and pale; otherwise the fundi appeared to be perfectlynormal. The visutal fields of the right eye showed a loss in the lowernasal quadrant and an arcuate scotoma reaching from the blind spotto 45 degrees below the horizontal. The left eye showed a markedconcentric constriction. Although the visual field findings in the righteye were reminiscent of glaucoma fields, as mentioned also by Lohlein,no data on the intraocular pressure were given in the paper. Heine16noted a marked restriction of the visual field in one of his cases(Case 6) anid a central scotoma in another (Case 9). Both patients hadgrayish discs. Godtfredsen's patient2" had a concentric constriction ofhis fields, as did Adriaenssen's patient24 with macular dystrophy.

WN'e have found some concentric constrictions in our patients as


reported above, but in evaluating the visual field findings in thesepatients it must be pointed out that it has been possible to obtain onlyone field test. This reduces the value of the tests, especially of those inwhich there were concentric constrictions. Nevertheless, a tentativecomparison of the results of the field tests with the ERG findings wasmade and it was noted that there appeared to be no correlationbetween the two. Six patients with normal peripheral fields were ratedas belonging to the "above average" ERG group, six as belonging tothe "below average" group.2 Among these were some of the patientswith the lowest ERGs. Only two of the patients with markedly con-stricted fields fell into the "above average" ERG group; five ranged inthe "below average" group, but none were extremely low. Very detailedretinal function testing in patients with myotonic dystrophy is plannedas soon as the necessary equipment becomes available.

CONCLUSIONS

The widespread involvement of the eye in myotonic dystrophy forcesone to assume that this involvement is not coincidental. We agree withGodtfredsent6 that myotonic dystrophy represents an entity which maybe grouped with the abiotrophies of the type of Laurence-Moon-Biedl'sand Refsum's syndromes and others, and that it is due to a polyphenicgene, as claimed by Franceschetti and coworkers.19

It would appear that myotonic dystrophy affects not only neuro-sensory epithelial systems, but also those of the lacrimal gland,' thegonads, and possibly also of the ciliary body. This does not resolve theultimate problems of whether the basic defect in myotonic dystrophydoes or does not reside in the midbrain, and of how the musculardystrophy ties in with the other anomalies. The answer to these prob-lems awaits further clinical and, especially, biochemical studies.

SUMMARY

The results of the ophthalmic examination of 25 patients with myo-tonic dystrophy are presented. Ptosis of the upper lid was noted in 21of them. Aside from this well-known sign, eight patients had blepha-ritis; there was a corneal involvement in a number of them, and the

*Hauptmann17 was very much impressed by excessive lacrimation and salivationin patients with myotonic dystrophy and considered these to be the result of anirritative state of the vegetative nervous system. Six of our patients did indeedcomplain of epiphora, but we were even more impressed by our positive findingsin the Schirmer test.

268


Sclhirmer test was positive in 20 ouit of 50 eyes. Lens changes typicalof myotonic dystrophy were seen in one form or another in everypatient. The intraocular pressure was quite low, the average for thegroup being 10 mm.Hg. The discs appeared normal in shape, color,and outline in all patients but definite anomalies of the macular areawere seen in six patients. These anomalies took in general the form ofstreak-like white and pigmented lesions. Four patients had grossclumpy pigmentation in the retinal periphery. The ERG was grosslyabnormal in virtually all patients, regardless of the appearance of theirfundi, and dark adaptation tests indicated a definite reduction inretinal sensitivity.

It is evident from the above that there is a widespread involvementof the eye in the diseased process of myotonic dystrophy. It wouldappear that this process relates not only to the neurosensory epithelium-suggesting that myotonic dystrophy should be classified with suchhereditary abiotrophic conditions as Laurence-Moon-Biedl's syndromeand Refsum's syndrome-but also to other epithelial structures.

REFERENCES

1. Tlhompson, H. S., NI. WV. Van Allen, and G. K. von Noorden, The pupil inmyotonic dystrophy, Invest. Ophth., 3:325-38, 1964.

2. Burian, H. NI., and Charlotte A. Burns, Electroretinography and dark adapta-tion in myotonic dystrophy, Am. J. Ophth., Niay, 1966, in prcss.

3. Wohlfart, G., Dystrophia myotonica and myotonia congenita: histopathologicstudies with special reference to changes in the muscle, J. Neuropath. &Exper. Neurol., 10:109-94, 1951.

4. Davidson, S., The eye in dystrophia myotonica with a report on electromyo-graphy of extraocular muscles, Brit. J. Ophth., 48:183-96, 1961.

5. Pendefunda, G., P. Cernea, and G. Dobrescu, Manifest'arile oculare in miotoniadistrofica Steinert, Oftalmologia (Bucarest), 7:219-24, 1964.

6. Allen, J. H., and C. G. Barer, Cataract of dystrophia myotonica, Arch. Ophth.,24:867-84, 1940.

7. Maillard, Ein Fall von degerativer Hornhauttriibung bei Myotoniekatarakt,Klin. Nlonatsbl. Augenh., 77 (2):647-9, 1926.

8. Verrey, F., TMyotonie dystrophique (maladie de Steinert) avec alterationmaculaire degenerative, Ophthalmologica, 114:281-4, 1947.

9. Vos, T. A., 25 years dystrophia myotonica (D.M.) (Netherlands Ophthalmo-logical Society, 143rd meeting, Rotterdam 1959), Ophthalmologica, 141:37-48, 1961.

10. Kuhn, E., and H.-J. Piesbergen, Hypotension des Bulbus und Katarakt beimyotonischer Dystrophie, Klin. Monatsbl. Augenh., 130:329-34, 1954.

11. Brand, I., Intraokulare Hypotonie bei MIyotonikern, Ophthalmologica, 129:81-8, 1955.

12. Curschmann, H., Myotonische Atrophie, in Bumke and Foerster, eds., Hand-buch d. Neurol., vol. 16, p. 485. Springer, Berlin, 1936.

13. Kambara, G. K., Choroidal metastasis of a testicular chorionic endothelioma,report of a case, Arch. Ophth., 41: 587-98, 1949.

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14. Radnot, M., Die Wirkung der Kastration auf den intraokularen Druck,Ophthalmologica, 125:171-4, 1953.

15. Fleischer, B., Ueber myotonische Dystrophie mit Katarakt, eine hereditare,familiare Degeneration, Graefes Arch. Ophth., 96:93-133, 1918.

16. L6hlein, W., Friihkatarakt bei atrophischer Myotonie, Klin. Monatsbl. Augenh.,52(I):453-7, 1914.

17. Hauptmann, A. (a) Die atrophische Myotonie, Deutsche Ztschr. Nervenh.,55:53-94, (1916); (b) Der heutige Stand der Lehre von der "myotonen"Dystrophie mit Katarakt, Klin. Monatsbl. Augenh., 60(I):578-92, 1918.

18. Heine, L., Ueber Tetanie-und Myotonie-Katarakt, Z. Augenh., 55:1-15,1925.

19. Franceschetti, A., J. Frangois, and J. Babel, Degenerescence tapeto-retinienneet dystrophie myotonique (maladie de Steinert), in Les heredo-degene-rescences chorio-retiniennes (dege'nerescences tapeto-retiniennes), Vol. II,pp. 1079-84. Paris, Masson, 1963.

20. Walsh, F. B., Clinical Neuro-ophthalmology, 2nd ed., p. 769. Baltimore,Williams & Wilkins, 1957.

21. Verwey and Legras, Myotonia atrophica, Ziekte van Steinert. Nederl. tijdschr.geneesk., 77(IV):4525-35, 1933.

22. Begaux, C., and G. Decock, La degenerescence de la dystrophie myotonique.Mod. Probl. Ophth., 1:267-76, 1957.

23. Magistretti, quoted after Franceschetti, et al.1924. Adriaenssen, A., Dystrophie myotonique et degenerescence maculaire juvenile,

Ann. ocul., 196: 1140-53, 1963.25. Slatt, B., Myotonia dystrophia: a review of 17 cases, Canad. M.A.J., 85:250-

61, 1961.26. Godtfredsen, E., Concurrence of dystrophia myotonica and dystrophia pig-

mentose retinae, Acta psychiat. et neurol. scandinav., 24:435-41, 1949.27. Igersheimer, J., The relationship of lenticular changes to mongolism, Tr. Am.

Ophth. Soc., 49:595-624, 1951 (see Table 2 on p. 610).28. Bajaj, N. L., Myotonia atrophica with retinitis pigmentosa, J. Indian M. A.,

43:134-5, 1964. Quoted after Excerpta Medica, XII(19):172, 1965.

DISCUSSION

DR. FRANCIS H. ADLER. Drs. Burian and Burns have provided us with anexcellent account of the eye involvement in 25 patients with establishedmyotonic dystrophy, which should quickly dispel the usual view thatcataracts are the only ocular pathology found in this distressing disease.Three different types of myotonia are recognized, and at present there is nounanimity of opinion as to whether they represent different diseases or aremerely variations of the same entity. They are known respectively asdystrophia myotonica, myotonia congenita, and paramyotonia congenita. Iassume that all of the patients under discussion this morning belong to thefirst group, dystrophia myotonica.

Myotonia may be defined as a state of delayed relaxation of skeletalmuscle following a contraction of adequate power. It may follow contractioninduced voluntarily or produced passively by mechanical, electrical, orchemical stimulation, and (especially in paramyotonia congenita) by theapplication of cold. It is not known precisely where the trouble resides, butat present the majority of workers favor the sarcoplasm and not the motor

Ocular Changes in Myotonic Dystrophyend-plate. Numerous theories based on present conceptions of the mechan-ism of muscular contraction which result from the interaction of actin andmyosin have been proposed. The enzyme chemists probably will have ananswer to this problem in the near future.The solution of dystrophia myotonica will probably result in an increased

knowledge of myasthenia gravis, for in many ways these two diseases areopposites; in dystrophia myotonica the symptoms are worse in the earlymorning, whenever the patient initiates a movement, and the myotoniadisappears on exercise; in myasthenia gravis the reverse is true. The electro-myographic picture contrasts markedly in the two conditions: in myotoniathe discharge from the muscles is spontaneous and exaggerated, whereas inmyasthenia the discharge is only elicited after the injection of Tensilon; inmyotonia the typical "interference pattern" is met with as in all dystrophies.Quinine is most effective in the relief of myotonia and makes myastheniaworse: "Quinine may throw the individual into a myasthenic crisis" (F.Walsh, Clinical Neuro-ophthalmology, 2nd ed., p. 780, Baltimore, Williams& Wilkins, 1957). In myotonia the muscle itself is probably the site of theinitial disturbance; in myasthenia it is probably the motor end-plate.

It seems strange to me that the one ocular condition myotonia and myas-thenia have in common is ptosis. In myasthenia the ptosis is due to levatorweakness. Is this true of myotonia?The authors do not mention weakness of the orbicularis muscles. Walsh

(ibid., p. 769) points out that involvement of the orbicularis oculi mayaccount for the infrequent blinking, but states that the eyelids can alwaysbe closed at will, although occasionally from myotonia there may be delayin opening them. Other authors have found weakness of the orbicularis aswell as ptosis, and Caughey (J. Caughey and N. Myrianthopoulos, Dys-trophia Myotonica and Related Disorders, p. 28, Springfield, Thomas, 1963)states that "weakness of the orbicularis oculi muscles is an almost constantfinding, but we have known these muscles to be little affected."

Paralysis of individual ocular muscles is rare, but both the present authorsand Walton and Nattrass (Brain, 77: 169, 1954) found marked restrictionin gaze movements, i.e. voluntary versions. I would be most interested toknow if reflex movements were similarly affected. What, for example, arethe movements induced by optokinetic nystagmus like?

As to the lens changes, it should be pointed out that these may occurlong before the patient shows any signs of myotonia or weakness, and thisdisease should be thought of in every young individual who developscataracts. In this connection and in connection with the fundus changesdescribed by Burian and Burns I wish to briefly report a patient who hasbeen under my care for the past 22 years.

Lorraine V., seen April 7, 1944, aged 24 years, complained of poorvision O.U. Had been told 3 years previously by Dr. Maxwell Langdon thatshe was developing cataracts. In December, 1942, she had a thyroidectomybecause of a toxic thyroid. Vision with best correction was 6/60 and 6/100.

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The lens changes wvere chiefly posterior capstular opacificationi with highlyiridescent spicules in the posterior and to a lesser extent in the anteriorlens cortex. A letter was sent to her family physician stating that she hadbilateral cataracts which were probably of metabolic origin but which werenot the usual type seen in hypoparathyroidism. Left eye was operatedOctober 19, 1945, anid the right January 23, 1946. Because of her age I didan extracapsular extraction with complete iridectomies in each eye. OInApril 27, 1946, I did a discission of the capsular remains in the right eye.The visionl with correction was 6/6 and 6,/6- and remained so until 1964.Her funcdi were normal as far as could be seen through some capsuleremains in the pupil space.

Her eyes gave her no bother and I saw her routinely once or twice avear. In 1949 I prescribed contact lenses for her which she wore withcomfort. Beginning in 1953 she had acquired a rather strange posture, andI noted it in my records. I assumed however it was an affectation. It wasa kind of slouch with the abdomen thrust forward and the shoulderselevated. About this time she also began to have chalazia, and between1955 aind 1964 I treated 14 different chalazia, most of which I had to openand curette. The lids constaintly showed a marginal blepharitis for whichantibiotic ointments were usually prescribed. The contact lenses werereplaced with bifocal glasses. The strange posture increased until it becameevident that it was due to structuiral changes in her spine or to some orgailicdisease which was making it difficult for her to walk. Changes in her face andmanner of speaking, followed, and from a very attractive, alert girl shebecame a most unicattractive, changed personality.

In 1964 her visual acuity for the first time fell from 6/6 and 6/6- cc.to 6/9 anid 6/9-. No changes were seen in the eyegrounds to account forthis, but as stated previously the visibility was somewhat limited becauseof capsular remains. She did not return for examination until February 9,1966, anid her vision had then fallen to 6/22 in each eye and could not beimproved. Her eyegrounds now showed narrowing of her retinal arteries,abnormal dilatations in the veins, and scattered cotton-wool patches through-out the posterior poles. I then found for the first time that she was beingtreated for myotonic dystrophy and that her father had died several yearspreviously of that disease. Consultation with her neurologist, Dr. GabrielSchwarz, confirmed mv belief that eyeground changes did not occur inmyotoinic dystrophy. He had never seen changes in any of his patients andno mention of such changes was found in Walsh's text. I felt the chanlgeswere suggestive of a collagen disease, and Dr. Schwarz informed me thatshe had been on Pronestyl which can produce lupoid reactions in certainsusceptible people. She had been given 250 mg. Pronestyl four times a daysince April of 1964. At the same time she had been on small doses ofprednisone 5 mg. four times daily since November, 1965. The Pronestylwas stopped. By April 5, 1966, the vision had improved in the left eyeto 6/12, but remained the same in the right. The cotton-wool patches had

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disappeared but the arteries were still thin threads. The acuity in the righteye gradually became worse, while that of the left improved. On May 24,1966, her best acuity was 6/60 R and 6/9 L cc. The fundus on the rightside was no longer visible due to corneal opacification which has nowoccurred along with filamentary keratitis in this eye. The cornea of the leftis normal and the fundus shows no changes except extremely narrow bloodvessels.The patient is evidently going downhill rapidly. There is marked atrophy

of the hands, purpuric eruptions on the right forearm, difficulty in masticat-ing and talking, and the lips remain open with saliva dripping from themouth.

I am not sure whether the retinopathy developed as a result of the diseaseor the drug used to treat it. The fact that the vision improved in the lefteye when the drug was stopped suggests of course that the drug wasresponsible. The changes which the authors of this paper found and believeto be specific for this disease may be present but I cannot detect them. Themedia are not sufficiently clear to visualize faint pigment changes and linesthey describe. I would like to ask them if any of their cases had been ontreatment with Pronestyl or similar drugs?

DR. HERMANN M. BURIAN. It is a great joy to have one's paper discussedby Dr. Adler, since he always adds so much to one's presentation. The casehe reported is surely most fascinating and instructive.

In commenting on Dr. Adler's discussion and in answering his questionsI wish to say, first of all, that we are aware of the orbicularis changesreported in the literature but were not impressed with them in our material.We have not seen a case of entropion in our patients, though entropion isfrequently mentioned in other case reports.

In regard to the reflex movements of the eyes, I might say that theoptokinetic nystagmus was normal in the patients whom we tested for it.None of our patients was on any kind of medication which could accountfor the fundus changes.

Finally, I might add that one patient-a 50-year-old woman not includedin our series-recently had cataract extractions. There was no difficulty inremoving the lenses intracapsularly. In spite of the relatively young ageof the patient, the suspensory ligaments of the lenses broke quite readily.

I should like to thank Dr. Adler for his kind and illuminating discussion.

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