with yellowplaques atrophic · with his left eye. the patient had no history of previous eye...

British Journal of Ophthalmology, 1980, 64, 127-134

A patterned macular dystrophy with yellow plaquesand atrophic changesPAUL CORTIN, DESMOND ARCHER, IRENE H. MAUMENEE,KATHY FEIOCK, AND PERRY SPEROSFrom the Wilmer Institute, Baltimore, Maryland, and the Department of Ophthalmology,Queen's University, Belfast

SUMMARY Three middle-aged male patients are described with a peculiar patterned dystrophy ofthe macula. The basic lesions are discrete yellow plaques typically confined to the macular area andradiating from the fovea. They appear to be located at the level of the retinal pigment epithelium(RPE). With the passage of time some of the yellow plaques altered in extent and configuration,and atrophic changes appeared or extended. Visual acuity and electrophysiological tests are eithernormal or only moderately affected. The lesions appear to be distinct from the patterned dystro-phies of the retina already described and from other conditions characterised by yellow or whitedeposits at the level of the RPE.

Several varieties of patterned dystrophy of theretinal pigment epithelium (RPE) have been des-cribed. They include Sjogren's reticular dystrophyof the retinal pigment epithelium,1' 2 macroreticulardystrophy of the retinal pigment epithelium,3 andbutterfly-shaped pigment dystrophy of the fovea.4The lesions are inherited, bilateral, and symmetricaland occur at the level of the RPE. The patterneddystrophies of the RPE do not significantly altervisual functions, and psychophysical and electro-physiological tests are generally only slightlyaffected.

Recently macroreticular, butterfly-shaped, andpossibly reticular dystrophy of the RPE have allbeen observed in one family, suggesting a linkbetween the patterned dystrophies of the RPE.5This report describes 3 patients with an unusualbilateral and symmetrical dystrophy of the macularregion characterised by discrete, yellow, plaque-likelesions at the level of the RPE and central atrophicchanges of the outer retina.

Case reports

PATIENT 1A 57-year-old male was seen by one of us (D.A.) inFebruary, 1974 with a 6-month history of deteriora-tion of vision in his left eye. He noticed that the'middle of the word disappeared' when reading

Correspondence to Dr P. Cortin, Ophtalmologie, CHUL,2705, boul. Laurier, Ste-Foy, Quebec, Canada, G1V 4G2.

with his left eye. The patient had no history ofprevious eye disease or defective night vision, andno member of his family had any significant eyecomplaints.On examination the best corrected visual acuity

was 6/6 right eye and 6/18 left eye. The anteriorsegments of the eyes were normal apart from anunusual vascular malformation of the right iris,which was considered an incidental finding. Eachfundus showed oval or oblong, yellow-whiteplaques arranged about the macula in a spoke-likeconfiguration often impinging on the fovea (Fig. 1).The lesions were relatively discrete and associated

only with subtle proliferative and atrophic changes.in the nearby RPE. Fundus biomicroscopy andstereoscopic photography indicated that the plaque-like lesions were slightly raised and located at thelevel of the RPE. There was no evidence of inflam-mation of the retina, choroid, or posterior vitreous.The left eye showed multiple, small, discrete,

white deposits within a central circular zone ofpigment epithelial atrophy at the fovea. Severalyellow-white plaques radiated from the centralatrophic hub (Fig. 2). Fluorescein angiography ofboth posterior fundi (Figs. 3, 4) showed clearlydefined areas of hyperfluorescence consistent withan abnormality of the RPE. The fluorescent defectswere more widespread than would have beenpredicted from ophthalmoscopy. The discreteyellow-white plaques remained hypofluorescent forthe most part throughout angiography, and,although some staining of the adjacent RPE was

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Paul Cortin, Desmond Archer, Irene H. Maumenee, Kathy Feiock, and Perry Speros

Fig. 1 Photograph right fundus, patient 1 (1974).Discrete plaques measuring one-third to one-half disc-diameter (DD) in size radiate from the foveal region.

-obvious in the late phases of angiography, there-was no evidence of dye extravasation beyond theretinal pigment epithelial barrier into the outerTetina.

Punctate hyperfluorescent defects were also notedbeyond the macula in each eye, indicating a more-widespread involvement of the RPE.

Static and kinetic perimetry (Tiubinger) revealed-a relative central scotoma in the right eye and a-small absolute central scotoma in the left eye. TheFarnsworth-Munsell 100 hue test revealed nospecific colour vision abnormality, but the electro-*oculogram (EOG) was subnormal in each eye, i.e.,1-5 right and left (lower limit of normal is 1-8 forlaboratory conditions). The photopic and scotopic-electroretinographic responses were within normallimits. A genetic survey did not reveal any similarlesions in members of the family examined.The fundus lesions were observed over a period

of almost 4 years, during which time most of the.oblong, yellow-white plaques either faded, dimi-nished in size, or disappeared.

In one or two areas the plaques extended or

Fig. 2 Photography left fundus, patient 1 (1974).Plaque-like lesions are arranged about the centralcircular area ofpigment epithelial atrophy.

increased in size and in 1 eye several fresh, whitedeposits occurred within and superior to themacula (Fig. 5, arrows). The new plaques weremorphologically and angiographically identical tothose initially noted 4 years previously. An atrophiccircular lesion of the RPE developed at the rightfovea and intensified and increased in size at theleft fovea (Fig. 6). Fluorescein angiography showeda slight increase in the area of defective pigmentepithelium at the macula, but there was no evidenceof fluid accumulation either in the subpigmentepithelial or subretinal spaces. Visual fields showedsome intensification of the central and paracentralscotomata in each eye, though visual acuity re-mained 6/6 right and 6/18 left. Electrophysiologicaltests revealed no progression of the functionalabnormalities.

PATIENT 2A 41-year-old male was referred to one of us (D.A.)in February 1975 complaining of slight deteriorationof vision in both eyes and in particular the left eye.The patient had attended the Eye Clinic in 1966

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A patterned macular dystrophy with yellow plaques and atrophic changes

Fig. 3 Venous phase fluorescein angiogram offundus Fig. 4 Late phase fluorescein angiogram offundusshown Fig. 1. There is a discrete abnormality of the shown Fig. 2. The macula shows a mottledretinal pigment epithelium involving the macula. The hyperfluorescence with some staining of the retinalplaque-like lesions are mostly hypofluorescent. pigment epithelial layer.

Fig. 5 Photograph right fundus patient 1 (1977). Some ofthe plaque-like lesions have faded, others have extended.Fresh lesions have occurred above the macula (arrows).

with recurrent attacks of bilateral episcleritis, andvisual acuity at that time was recorded as 6/5 rightand left. The patient gave no history of defectivenight vision and was in good general health.On examination the best corrected visual acuity

was 6/9 right and 6/12 left. Static and kineticTubinger visual fields showed no abnormality, andcolour vision was normal by the Farnsworth-Munsell 100 hue test. The EOG was normal inthe right eye (2 0) but significantly reduced in theleft eye (1-17). Photopic and scotopic electroretino-graphic recordings were within normal limits foreach eye.Both fundi showed circular or oblong, yellow-

white plaques at the macula (Figs. 7, 8) situated atthe level of the RPE. There were scattered areas ofretinal pigment epithelial atrophy and proliferation

Fig. b Photograph left Jundus, patient 1 (Y1/9).The plaque-like lesions have faded and the centralcircular atrophic area has increased in size.

at and near some of the plaques and a well-defined,discrete circular zone of pigment epithelial atrophyat each fovea. Fluorescein angiography confirmedthe presence of a retinal pigment epithelial abnor-mality at and surrounding each fovea. The denseyellow-white plaques and foci of pigment accumu-lation were hypofluorescent, and areas of pigmentepithelial atrophy were hyperfluorescent (Figs. 9, 10).Over a period of 21 years the yellow-white

lesions became less distinct and the central circularzone of retinal pigment epithelial atrophy becamemore marked. Fluorescein angiography did notindicate any significant increase in the extent of thelesion, which remained confined to the macula. Asurvey of the patient's family revealed no charac-teristic macular lesions; however, 1 brother hadextensive drusen of both fundi, a widespread atrophy

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Fig. 7 Photograph right fundus, patient 2 (1975).Faint white plaques surround a circular zone ofpigmentepithelial atrophy.

-ig. 8 Photograph left fundus, patient 2 (1975). Welldefined white plaque-like lesions radiate from a centralcircular area ofpigment epithelial atrophy.

lig. 9 Venous phase fluorescein angiogram of fundus Fig. 10 Late-phase fluorescein angiogram offundusshown Fig. 7. Discrete pigment epithelial defects shown Fig. 8. The plaque-like lesions are mostlyfluoresce brightly. hypofluorescent and there is some staining of the

affected retinal pigment epithelial layer.of the RPE, and a visual acuity diminished to 6/24right and 3/60 left. The patient's father also had poorvision and was able to read only large print using amagnifying glass from the age of 60. The patient'sfather and mother were first cousins.

PATIENT 3A 52-year-old male was referred to one of us(I.H.M.) in April 1974. He had noticed about theage of 40 that vision had decreased in each eye.During the 3 years prior to presentation, he hadbeen treated for asthma with prednisone 5 mg perday and for kidney stones with allopurinol. Onexamination the best visual acuity was 6/18 rightand 6/12 left. Routine eye examination was normalapart from the changes noted on funduscopy. Theright fundus (Fig. 11) showed a pigmented ring ofless than 1 disc diameter (DD), within which athinned retina and choroidal vessels were seen

Fig. 11 Fundus photograph right eye, patient 3. Apigmentary ring delineates a central area of retinalpigment epithelial atrophy. Yellow stripes are radiallyarranged around the atrophic zone.

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Fig. 12 Left fundus photograph, patient 3. Radiatingyellow stripes are arranged around the fovea in apetaloid fashion.

Fig. 14 Late phase fluorescein angiogram offundusshown in Fig. 11. The yellow stripes are hypofluorescentand are highlighted against the hyperfluorescentpigment epithelial defects.

with the slit-lamp. Around the pigmented ring theretina showed a greyish yellow material depositedin a radial fashion deep in the retina or at the levelof the RPE.The left macula (Fig. 12) also demonstrated

yellowish deep-seated deposits which were moredistinct than those noted in the right fundus. Theabnormal material radiated in a petaloid fashionfrom the region of the left fovea. There was noevidence of microcystoid degenerative changes.Over a period of 20 months 1 of the deposits (notedat l l o'clock) partially faded, leaving a deep-seatedpigmentary line (Fig. 13).During fluorescein angiography the right macula

(Fig. 14) showed a central dark zone within thepigment ring noted on ophthalmoscopy. This, inview of the biomicroscopic findings, suggested a

Fig. 13 Leftfundus photograph, patient 3, taken 20 monthsafter fundus photograph shown in Fig. 12. The 11 o'clockstripe has faded leaving a pigmentary line. The 4 o'clockstripe may have extended (some artefacts are present).

Fig. 15 Early venous phase angiogram offundusshown in Fig. 12. The yellow stripes are strikinglyhypofluorescent or nonfluorescent.

localised atrophy of the choriocapillaris. Peripheralto the ring a 100 wide circle of hyperfluorescence wasevident. Stripes of hypofluorescence correspondedmore or less to the yellow deposits highlighted onthe hyperfluorescent background. On the left side(Fig. 15) fluorescein angiography showed six non-fluorescent, radially orientated stripes contrastingagainst the hyperfluorescent background.

Patient 3's 54-year-old only brother noticeddecreased vision in his left eye at age 26. Vision isthought to have been stable since. There was nometamorphopsia or photophobia; however, thepatient admitted to some degree of night blindness.Routine ocular examination showed no structuralabnormalities apart from the lesions noted at thefundi. The corrected visual acuity was 6/7 5 rightand 6/36 left. The right fundus showed a small

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Fig. 16 Right fundus photograph ofpatient 3's brother.There is a small perifoveal atrophic area. Ill-definedyellow deposits are present and a zone ofperipapillaryatrophy is noted.

Fig. lb Left fundus photograph patient 3's brother.There is marked peripapillary chorioretinal atrophyand a macular scar.

circular zone of retinal atrophy nasal to the fovea.There were some ill-defined stripes of yellowdeposits which were hypofluorescent during fluo-rescein angiography (Figs. 16, 17). The left fundusshowed an atrophic maculopathy with peripapillarychoroidal atrophy and peripheral postequatorialpigmented lesions (Figs. 18, 19, 20), a picturereminiscent of the presumed ocular histoplasmosissyndrome. During angiography a focal area ofhyperfluorescence was noted at the left maculaindicating a defect of the retinal pigment epithelium(Fig. 20).No abnormality was detected on routine exami-

nation of patient 3's three children except for 2drusen at the right posterior fundus of his 16-year-old daughter (Fig. 21).

Patient 3's parents were not examined. Hisfather was said to have normal vision, but his

Fig. 17 Mid venous phase angiogram offundus shownmid venous. There are discrete hyperfluorescent pigmentepithelial defects. The yellow plaques are hypofluorescent.

Fig. 19 Left superonasal peripheral fundus patient 3'sbrother. Postequatorial pigmented lesions are present.

Fig. 20 Late venous phase angiogram offundus shownmid venous. There is striking peripapillary and macularhyperfluorescence. The features are reminiscent of thepresumed ocular histoplasmosis syndrome.

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Fig. 21 Right fundus photograph of 16-year-olddaughter ofpatient 3. Two small drusen are presentbelow the macula.

mother used a magnifying glass in addition to herbifocals after the age of 60.

Extensive psychophysical tests were performedby one of us (K.F.) on patient 3, his brother, andhis 3 children. The perimetric studies were donewith the Tubinger and Ferre-Rand perimeters.Essentially, they showed central scotomas in the2 brothers and relative parafoveal scotomas inpatient 3's daughter. The dark adaptation curveswith the Tiibinger perimeter were somewhat sub-normal in the 2 brothers, in accordance with thesymptoms. Colour tests were within normal limitsexcept for the left eye of the brother.The ERGs were recorded by one of us (P.S.). A

modified Rabin and Berson's technique6 was used.They showed reduced amplitudes and prolongedimplicit times of both photopic and scotopicERGs in patient 3 and his brother. ERGs werenormal in the children. Normal EOG ratios werefound in both brothers.

Discussion

Three patients with unusual but characteristicallypatterned lesions of the macula are presented. Thepatients are all male and suffered only mild, moder-ate, or no disturbance of visual functions. Theexact age of onset of the lesions was difficult toestablish, but it probably occurred between theages of 30 and 50. The basic abnormality was anoval or oblong, yellow, plaque-like lesion confinedto the macular area. The plaques were multiple,relatively discrete, about one-third to one-half adisc diameter in size, and typically arranged in aradial pattern about the fovea. Fundus biomicro-scopy and stereophotography confirmed that thelesions were slightly elevated and located at the

level of the RPE. The neighbouring retina showed avariety of RPE changes, some atrophic and someproliferative. The earliest lesions, which wereusually asymptomatic, had a uniform yellow-whitehue, but with time usually faded, disappeared, orwere replaced by an area of RPE atrophy or proli-feration. A circular area of atrophic retinal pigmentepithelium characteristically developed at or nearthe fovea in all cases, and at this stage there wasgenerally some abnormality of central visualfunction. Other changes included circular areas ofretinal thinning and choriocapillaris loss. In 1patient fresh macular and extramacular lesionsdeveloped over a period of 2 to 3 years. Theseadditional lesions had identical characteristics tothose plaques noted at initial examination.The existence of some similar lesions in the right

eye of patient 3's brother suggests that the conditionmay be familial, but it is not possible from thecurrent data to establish a mode of inheritance. Itit left to other workers in the future to be moreexplicit on the genetics, if indeed further cases wouldconfirm our present strong suspicion that it is aheritable condition.No histopathological studies have been under-

taken of the lesions in question and their exactnature is not known. However, ophthalmoscopicand angiographic evidence suggest that the diseaseprimarily affects the RPE, and the typical yellowplaques probably represent a deposition or accumu-lation of some substance within the RPE or in itsimmediate vicinity. Despite the discrete morphologyof the individual plaques there is reason to suspecta diffuse abnormality of the RPE in some patientson account of the widespread abnormalities onfluorescein angiography and the significant EOGfindings. The retinal receptors appear relativelyunaffected, at least until late in the disease process.The lesions described are distinctive and mor-

phologically different from the other varieties ofpatterned dystrophy of the macula. The radiallyarranged yellow plaques are not typical of thereticular dystrophies or the butterfly dystrophy ofthe fovea, and no atrophic changes have beendescribed in latter conditions. The yellow plaquesresemble confluent drusen in that they occur at thelevel of the RPE, are discrete, and predominantlyaffect the posterior fundus. However, the yellowplaques show little tendency to enlarge concen-trically and are characteristically hypofluorescentduring angiography. The radial disposition of thesubretinal plaques is quite different from the generaldistribution of drusen, and no obvious decompen-sation of the retinal pigment epithelial barrier ordevelopment of a disciform response has been noted.The lesions characteristic of patterned dystrophy

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described in this report also differ fundamentallyfrom those typically of fundus flavimaculatus intheir hue, size, and distribution. The yellow pat-terned lesions show some of the characteristics ofthe deposits encountered in vitelliform maculardegeneration (Best's disease). They are both yellow,situated at the level of the RPE, and associated withrelatively mild changes in central visual functions.The appearance of fresh lesions at the posterior poleof the eye during the evolution of the yellow plaquesmay also occur in vitelliform macular degeneration.The patterned dystrophy, however, differs fromvitelliform macular degeneration in that there is noevidence of a yolk-like lesion at any stage of thedisease process or layering of the abnormal deposits.In addition the electrooculographic changes invitelliform macular degeneration are more uniformand severe than those noted in our patients.A peculiar foveomacular dystrophy described by

Gass7 shows some of the clinical characteristics ofthe patterned dystrophy reported in this paper. Inboth groups of patients the condition began between30 and 50 years of age and affects vision relativelyslightly. The lesions in both conditions are sub-retinal, symmetrical, and slowly progressive. Thelesions described by Gass, however, are less regular,not disposed in a petaloid pattern, and have auniform, central pigmented spot at the fovea. Inaddition many of his cases are also associated witha more widespread disturbance of the RPE and tosome degree resemble hereditary drusen.Singerman et al.8 have recently described a

macular dystrophy in a large sibship and labelledthe condition dominant slowly progressive maculardystrophy. Some of the patients described in thisreport have macular lesions resembling the yellow

plaques described above and showed similarangiographic features. It may be that there is someoverlap in the cases described in our report andcertain of the members of their large sibship.Although the patterned dystrophy with yellow

plaques and atrophic changes resembles several welldocumented focal abnormalities of the RPE, itnevertheless has distinct morphological charac-teristics, a natural course and fundus findings, andit is probably justifiable to consider it as a separateclinical entity. The yellow plaques almost certainlyrelate to an abnormality or malfunction of the RPEand as such probably form a small part of the widespectrum of conditions which reflect a malady ofthis highly specialised layer.

References

1Sjogren H. Dystrophia reticularis laminae pigmentosaeretinae. Acta Ophthalmol 1950; 28:279-295.2Deutman AF, Rumke AML. Reticular dystrophy of theretinal pigment epithelium. Arch Ophthalmol 1969; 82:4-9.3Mesker RP, Oosterhuis JA, Delleman JW. A retinal lesionresembling Sjogren's dystrophia reticularis laminae pig-mentosae retinae. In: Perspectives in Ophthalmology 2:40-45. Amsterdam: Excerpta Medical Foundation, 1970.4Deutman AF, van Blommestein JDA, Henkes HE, Waar-denburg PJ, Solleveld-Van Driest E. Butterfly-shapedpigment dystrophy of the fovea. Arch Ophthalmol 1970; 83:558-569.5Hsieh RC, Fine BS, Lyons JS. Patterned dystrophies ofthe retinal pigment epithelium. Arch Ophthalmol 1977; 95:429-435.6Rabin AR, Bearson EL. A full-field system for clinicalelectroretinography. Arch Ophthalmol 1974; 92:59-63.7Gass JDM. A clinicopathologic study of a peculiar foveo-macular dystrophy. Trans Am Ophthalmol Soc 1974; 72:139-156.8Singerman LJ, Berkow JW, Patz A. Dominant slowlyprogressive macular dystrophy. Am J Ophthalmol 1977;83:680-693.

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with yellowplaques atrophic · with his left eye. the patient had no history of previous eye...

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