unilateral retinitis pigmentosa sine...

Brit. J. Ophthal. (1976) 6o, 354

Unilateral retinitis pigmentosa sine pigmento

JEROME T. PEARLMAN, JOAN SAXTON, AND GARY HOFFMANFrom the Department of Ophthalmology, Visual Physiology Laboratory, 7ules Stein Eve Institute,UCLA School of Medicine, Los Angeles, USAAND

STANLEY CARSONFrom the Department of Ophthalmology, USC School of Medicine, Los Angeles, USA

At the Fourth ISCERG Symposium, held inHakone, Japan, in I966 Straub (I966) reviewedthe subject of unilateral retinitis pigmentosa andmade a number of important observations. Up tothen only 34 cases of unilateral retinitis pigmentosahad been reported. Only one of them was of uni-lateral disease without pigment (Jacobson andStephens, I962). Rickers and Domarus (I974)stated that nearly ioo cases of unilateral retinitispigmentosa had been described since the firstreport in I865. They thought that the diagnosiscould be verified in only about 20 cases.

Straub emphasized the clinical value of electro-retinography (ERG) in establishing the truly uni-lateral nature of such cases, indicating that theERG response must be normal in the unaffectedeye. Others have long recognized that many casesof supposed unilateral retinitis pigmentosa wereactually instances of highly asymmetric bilateraldisease in which the 'normal' eye eventuallyshowed the disorder, but only much later. Frances-chetti, Frangois, and Babel (I963) showed that theERG response in such cases was impaired in botheyes. This significant clinical feature distinguishesgenuine unilateral disease from 'pseudounilateral'(that is, asymmetric bilateral) retinitis pigmentosa.Henkes (I964) found that the electro-oculogram

was bilaterally disturbed in many instances ofpresumed unilateral retinitis pigmentosa but normalin the unaffected eye in truly unilateral cases. Thusmeasuring the resting potential of the eyes as wellas the ERG is of value.

If unilateral retinitis pigmentosa is uncommon,cases without pigmentation are even rarer. Wereport here a case of unilateral retinitis pigmentosasine pigmento.

This study was supported by NIH grant EYoo331 from the NationalEye Institute (Bethesda, Maryland) and from the private contribu-tions of the Sklar and Phillips Families (Shreveport, Louisiana)

Address for reprints: Jerome T. Pearlman, MD, Jules Stein EyeInstitute, UCLA School of Medicine, Los Angeles, California90024

Case report

A 27-year-old White woman was first seen at theJules Stein Eye Institute on 7 March 1974 complainingof seeing spots before the left eye for the past threeweeks. She was taking oral contraceptives, but other-wise her past medical history was normal. There was nofamily history of consanguinity. Childhood diseasesincluded measles, mumps, and chicken pox. Her serologywas normal. She did not complain of the right eye andof only minimal symptoms in the left. Unaided visualacuity was 20/20 in each eye, and she did not wearspectacles.The findings on external examination were within

normal limits. Slit-lamp examination showed nothingbut a number of dot-like opacities in the anteriorvitreous of the left (affected) eye. Initially, these dot-like opacities were thought to be evidence of an inflam-matory aetiology of this condition. Such opacities,however, exist in the vitreous of patients with tape-toretinal degeneration (Berliner, I949). Their absencein the unaffected eye was interpreted as additionalevidence of the unilaterality of this patient's disorder.

OphthalmoscopyThe fundus of each eye was examined through pupilsdilated with i per cent tropicamide and io per centviscous phenylephrine hydrochloride ophthalmic solu-tions (Fig. i). The left eye showed some haziness ofthe vitreous; much attenuated retinal arterioles; and asubtle, patchy retinal pigment epithelial disturbancein the midperiphery. There was no convincing pallorof the left optic nerve head. The right fundus wasnormal. No pigmentary changes of salt and pepper orbone corpuscle type were noted. Intraocular pressureby applanation tonometry was i6 mmHg on each side.Special tests consisted of fluorescein angiography,Kodachrome fundus photography, colour vision tests,Goldmann fields, dark adaptometry, electroretino-graphy, and electro-oculography.

Fluorescein angiography of the left eye showed asignificant delay in the appearance of dye in the vasculartree relative to the right eye, with considerable attenu-ation of the retinal arterioles. Even the veins were ofsmaller calibre. Compared with the right eye, there wasa striking hyperfluorescence on the left side in the late

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Unilateral retinitis pigmentosa sine pigmento 355

FIG. 2 Fluioresceznfundus angiograms

(a) Normal right eye 25 secondsafter injection of dye

(b) Abnormal left eye 23-8 secondsafter injection of dye. Note unusualdegree of choroidal hyperfluorescencesurrounding darker, central maculararea, indicating diffuse abnormality ofretinal pigment epithelial layer

phase. No macular disturbance was noted, even on

magnification. Fixation was normal (Fig. 2b). A similarstudy of the right eye showed a normal transit and latephase (Fig. 2a).

Colour vision was normal in both eyes when testedwith AO H-R-R and Ishihara pseudoisochromaticplates. No mistakes were made. Goldmann fields ofthe right eye were within normal limits; those of the


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356 British Journal of Ophthalmology

FIG. i Fundusphotographs

(a) Disc and macula ofnormal right eye

(b) Disc and macula ofaffected left eye. Noteabsence of significantoptic nerve pallor andpresence of muchattenuated retinalarterioles


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(c) Periphery ofnormal right eye

(d) Periphery ofabnormal left eye

showing mottling inretinal pigment

epithelial layer. Nobone corpuscularpigment was seen

anywhere in left fundus


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358 British J7ournal of Ophthalmology

LEFT RIGHT

FIG. 3 Goldmannfields of normal right eye and abnormal left eye. Note constriction of all isoptres in OS and the absenceof central scotoma. Largest isoptre is IV-4; next is i-4; next is I-3; and smallest I-2 on the Goldmann perimeter

left eye showed pronounced constriction of the peri-pheral field compared with the right. The I-2 isoptreof the left eye was reduced to about six degrees (Fig. 3).

Dark-adaptation studiesDark-adaptation studies were made with the Goldmann-Weekers adaptometer with a one degree test objectflickering on and off at one-second dark and lightintervals. The test spot was located 5-5 cm below thefixation point on the instrument, and thus projectedi i degrees above the fovea on the subject's retina.Each test was conducted in the standard manner withpupils dilated by tropicamide i per cent and phenyl-ephrine hydrochloride io per cent viscous ophthalmicsolutions. The subject was exposed to pre-adaptingillumination of i8 lux (2800 abs) for five minutes.Each test lasted a total of 45 minutes. The tracingsshowed a normal cone onset for both eyes and a normaldevelopment of the rod portion of the curve for theright eye. The left eye showed an abnormal rod develop-ment and a raised threshold, beginning at about nineminutes and persisting for the duration of the test. Atthe end of the examination the final rod threshold forthe left eye was 1-3 log units higher than that of theright eye (Fig. 4).

ElectroretinographyERG studies were made in the routine manner of our

laboratory. After dark adaptometry patients dark-adapted for an additional 45 minutes. Burian-Allencontact lens electrodes were inserted under red lightillumination after instilling proparacaine hydrochlorideo0o5 per cent ophthalmic solution for corneal anaes-

thesia. White light stimuli of 20 ms duration recordedsingle and multiple flash responses. Dark-adapted

eyes placed in Maxwellian view received the flashesvia optical fibres from a tungsten lamp, with a Hartlineshutter and a series of neutral density filters to varystimulus intensity. Threshold responses were measured,beginning with subthreshold stimuli in single flashes.After about 30 seconds the next flash was presented.As the stimulus intensity increased the interval betweensingle flashes was lengthened to about one minute toensure the dark-adapted state. The intensity of thestimulus light was such as to generate a maximal b-wave; the same light was used for both eyes, whichwere always recorded simultaneously. The patient'stracings showed normal b-waves on the right side anda highly abnormal, but barely recordable b-waveresponse on the left side (Fig. 5).

Electro-oculographyElectro-oculography was performed with the patientsitting in a darkened room for 45 minutes. Skin electrodeswere attached at the medial and lateral canthi of each eyeand in the centre of the forehead. A baseline responsewas recorded after one hour of dark adaptation. Eachchannel of the recording instrument was calibrated at400 ,uV. The dark-adapted response was next measuredfor 12-5 minutes. With the eyes executing an excursionof 2o degrees at a distance of i -82 m from fixationtargets the amplitude of the dark response was 1000 FVfor the right eye and 6oo lzV for the left. Next, the light-adapted response was measured for I2-5 minutes. The9 minutes reading was the maximum light rise. Thenormal right eye showed excursion amplitudes of2200 ViV while the abnormal left eye showed the sameamplitude, or no 'light rise' at all. Thus the Ardenlight-to-dark ratio of the normal right eye was 2-2,or 220 per cent, while the abnormal left eye showed a


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10~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~2~~~ ~ ~ ~ ~ ~ ~~~ Rqteye

mm.i 5 10 15 20 25 30 35 40 45

FIG. 4 Dark adaptation record showing raised threshold of the left eye compared with normal threshold of right eye.Difference of I-3 log units in threshold indicates so-fold decrease in sensitivity of left eye. Initial cone portionsof two curves (between 5 and 8 min) were very similar. Dots and bars indicate normal mean (± 2 SD) values fortest in our laboratory

ratio of I-O or ioo per cent (Fig. 6). The EOG has beenperformed four times during the past i8 months. Sincedifferent instruments and protocols were used it isimpossible to compare precisely the several tests,except to confirm the constant abnormality of the lefteye as opposed to the normal right eye. The right eyehas shown no evidence of functional impairment sinceour first contact with the patient.

Discussion

The diagnosis of retinitis pigmentosa sine pigmentofrom purely ophthalmoscopic findings is rathermore difficult than in the more typical case of the

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FIG. 5 Electroretinographic record of single flashsimultaneously received by right eye (top) and left eye(bottom). Intensity used was equalfor both eyes.Normal right eye shows small a-wave and large b-wave;affected left eye shows severely impaired b-wave

disease with pigment deposition. Indeed, changesin the retinal pigment epithelial layer in the absenceof pigment deposition are remarkably subtleand may easily escape detection. Optic pallormay be minimal or absent, as in this patient.Arteriolar attenuation was obvious in our case butmay not be so in every case. Moreover, whenevaluating the significance of arteriolar attenuationthe possibility of a previous central retinal arteryocclusion must be considered. This condition, we

thought, could be ruled out in our case because ofthe patient's young age and the absence of anyhistory of sudden, severe loss of vision on theaffected side. Thus monocular constriction of theperipheral field in the presence of ipsilateralnightblindness may be the first diagnostic clue.Next, the finding of a grossly diminished b-waveor non-recordable ERG response on the one sideand a normal response on the other lends additionalweight to the impression of retinitis pigmentosasine pigmento. And, finally, a unilaterally abnormalEOG supports the diagnosis even more strongly.The amount of pigmentation in retinitis pigmen-

tosa is variable. Pigment deposition can be sparse,

moderate, or heavy-depending on any number offactors, including the patient's age, duration ofthe disease, and an individual proclivity, as itwere, to deposit intraretinal pigment. Quitelikely the sine pigmento state is one extreme of a

wide spectrum of pigmentary patterns found inthat group of diseases called 'retinitis pigmentosa'and not the manifestation of a separate or distinct

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360 British 7ournal of Ophthalmology

Calibration Dark (12-5min) Liqht (9min)

ODDrRLqht eye

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disorder. Our patient has been followed-up sinceMarch I974 and still shows normal retinal functionon the right side, but there is no guarantee that atsome future time she may not develop bilateraldisease or develop pigmentation on the currentlyaffected side. Nevertheless, for the present thepatient may be reasonably classified as an exampleof unilateral retinitis pigmentosa without pigmentbecause all diagnostic criteria have been met.

SummaryA patient presented with unilateral findings of

FIG. 6 Electro-oculographicresponse of both eyes after I2-5minutes of dark adaptation and 9minutes of light adaptation.Unaffected right eye shows normallight rise of over 200 per cent whileinvolved left eye shows no lightrise whatever

night blindness shown by impaired rod functionand dark adaptation, constricted visual fields withgood central acuity, a barely recordable electro-retinographic b-wave, and a unilaterally impairedelectro-oculogram. There were none of the pig-mentary changes usually associated with retinitispigmentosa. The unaffected right eye was normalin all respects. Therefore the case is most probablyone of unilateral retinitis pigmentosa sine pigmento.

We thank Mrs Nola J. Allston and Mr Robert Petrusfor their technical assistance.

References

BERLINER, M. D. (1949) 'Biomicroscopy of the Eye', vol. 2, p. 1439. Hoeber, New YorkFRANCESCHETTI, A., FRAN9OIS, j., and BABEL, J. (i963) 'Les heredo-degenerescences chorio-retiniennes',

p. 339. Masson & Cie, ParisHENKES, H. (I964) 'Proceedings of 3rd ISCERG Symposium', p. 327. Pergamon Press, OxfordJACOBSON, J. H., and STEPHENS, G. (i962) Arch. Ophthal. (Chic.), 67, 96RICKERS, j., and v. DOMARUS, D. (1974) Unilateral retinopathia pigmentosa. In 'Proceedings of the i ith ISCERG

Symposium, Bad Nauheim', ed. E. Dodt and J. T. Pearlman, p. 513. Junk, The HagueSTRAUB, w. (I966) Unilateral retinitis pigmentosa. 'Proceedings of 4th ISCERG Symposium', p. 278, vol. io Suppl.


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