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Central Areolar Pigment Epithelial Dystrophy
CENTRAL AREOLAR P I G M E N T E P I T H E L I A L DYSTROPHY C A R L L. F E T K E N H O U R , M.D.,
N E L S O N GURNEY,
M.D.,
J. G R A H A M D O B B I E , M.D., AND E A R L C H O R O M O K O S
Chicago, Illinois
At the turn of the century, Batten 1 and Stargardt 2 introduced the subject of fa milial disease of the macula. Since that time several hereditary macular dystro phies have been described and record ed. 3 - 1 8 Table 1 categorizes some of the more widely recognized dystrophies ac cording to mode of transmission. Early studies emphasized genetic and ophthalmoscopic characteristics. More recent studies have attempted to examine struc tural and functional déficiences by means of fluorescein angiography and retinal function analysis. Most of these dystrophies represent discrete nosologie entities. Variations do occur within these groups (for example, vitelliform), but these are now well recog nized. A few are less well defined (for example, Sorsby's pseudoinflammatory macular dystrophy) and may be easily confused with other hereditary or ac quired macular defects. Almost all of the dominant macular hereditary dystrophies are associated with visual impairment or abnormal retinal function studies at some stage of their development. Deutman 7 de scribed a new dominant macular dystro phy characterized by good vision and a benign course in which retinal function studies were abnormal. In our study, good visual acuity was generally preserved and retinal function studies were normal. There was no pro gression of the lesion. The macular leFrom the Northwestern University Medical School, Department of Ophthalmology, Chicago, Illinois. Presented at the American Ophthalmology Socie ty Meeting, Hot Springs, Virginia, May 30, 1975. Reprint requests to Carl L. Fetkenhour, M.D., Northwestern Memorial Hospital, 707 N. Fairbanks Court, Chicago, IL 60611.
sions were central, depigmented, sharply demarcated, and involved primarily the pigment epithelium. We are, therefore, calling this dystrophy central areolar pig ment epithelial (CAPE) dystrophy. M A T E R I A L AND M E T H O D S
We examined nine members of one family (Fig. 1), using stereoscopic color photography and fluorescein angiogra phy, electro-oculography, dark adapta tion, H-R-R color plates, and the Farnsworth-Munsell 100-hue test. Electroretinography was performed with a ganzfeld stimulator and blue, red, and white light stimuli. 1 9 Single urine sam ples were obtained from all affected fami ly members for Chromatographie amino acid analysis. CASE REPORTS
Case 1—The proband, a 13-year-old white boy (III-7), had sudden loss of visual acuity in the right eye. He denied previous ocular problems. Corrected visual acuity was R.E.: 20/200, and L.E.: 20/25. A well-circumscribed subretinal hemorrhage and edema were noted in the right macula (Fig. 1, A). The left macula revealed a 1-disk diameter zone of pigment epithelial atrophy with an excavation into the choroid (Fig. 2, B). Optic disks, retinal vessels, and peripheral retinas were normal. Fluorescein angiography of the right eye demonstrated a central macular leakage of dye surrounded by hemorrhage (Fig. 3, A) and in the left eye, hyperfluorescent show-through (Fig. 3, B) corresponding to the de pigmented macula. Electroretinography, electrooculography, and dark adaptation were normal in each eye. Color vision abnormalities in the right eye consisted of several missed H-R-R color plates and more than 600 errors arranged in a nonspecific pattern on the Farnsworth-Munsell 100-hue test. Color vision was normal in the left eye. The urine amino acid analysis was normal. Sixteen months after its onset, the macular hemorrhage resolved and visual acuity was 20/25 (Figs. 2, C and 3, C). This boy's mother (II-4) was killed at age 21 in an automobile accident. Family members reported that she had no visual impairment, but "retinal scars" had been detected in both eyes by previous exami ners.
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TABLE 1 MACULAR DYSTROPHIES ACCORDING TO MODE OF TRANSMISSION
Dominant
Recessive
Vitelliform Cone dystrophy Progressive macular atrophy Drusen Central choroidal Pseudoinflammatory Progressive foveal dystrophy Butterfly Benign annular concentric
Fundus flavimaculatus Reticular Central retinitis pigmentosa Grouped pigmentation
Case 2—A 32-year-old woman, the proband's ma ternal aunt (II-5), had visual acuity of 20/20 in both eyes and no ocular complaints. Macular depigmentation was noted in both eyes (Fig. 2, D). Otherwise, the retinal vessels and optic disk were normal. Fluorescein angiography revealed bilateral hyperfluorescence in each macula (Fig. 3, D). Electroretinography, electro-oculography, dark adaptation, and color vision were normal. Case 3—A 7-year-old girl, the maternal cousin (III-9) of the proband, was asymptomatic with visu al acuity of 20/20 in both eyes. She demonstrated similar bilateral central pigment epithelial defects (Fig. 2, E). The fundi were otherwise normal. Fluo rescein angiography again revealed bright showthrough of the underlying choroidal fluorescence (Fig. 3, E). All retinal function studies were normal, and the urine amino acid analysis was normal. Case 4—A 60-year-old man, the proband's mater nal grandfather (1-2), had no ocular complaints. Visual acuity was 20/20 in both eyes. Macular depigmentation (Fig. 2, F) was not as striking as in the other affected family members, but fluorescein angi ography (Fig. 3, F) revealed a similar hyperfluorescent show-through pattern. The urine amino acid analysis was normal.
o 3
4
X-Chromosome Linked
DISCUSSION
The clinical course of this pigment epi thelial dystrophy was characterized by childhood onset, good visual acuity, and nonprogression. With one exception these patients were asymptomatic. Normal reti nal function studies corroborated the be nign nature of the dystrophy and ruled out a diffuse retinal degeneration. No other dominant hereditary macular dys trophy has these characteristics. Vitelliform degeneration may present as an intact (vitelline) or "scrambled" (vitelliruptive) egg yolk lesion, or macular hemorrhage. Although visual deteriora tion is the rule and the electro-oculogram is classically decreased, recent studies 2 0 , 2 1 have disclosed normal electro-oculograms in patients with typical vitelliform lesions. However, we considered this a rare possibility.
O
5
.
7
6
Juvenile retinoschisis
Π
UNAFFECTED
W H
AFFECTED
©
REPUTEDLY AFFECTED PROBAND
9 10 8 X Fig. 1 (Fetkenhour and associates). Pedigree of family with central areolar pigment epithelial dystrophy; circles represent females and squares, males.
Α. Case 1, right eye (III-7).
C. Case 1, right eye (111-7) after resolution of macular hemorrhage.
E. Case 3, right eye (III-9).
B. Case 1, left eye (III-7).
D. Case 2, left eye (II-5).
F . Case 4, right eye (1-2).
Fig. 2 (Fetkenhour and associates).
Fig. 3 (Fetkenhour and associates). Fluorescein angiography. Α. Case 1, right eye (III-7). Β. Case 1, left eye (III-7). C. Case 1, right eye (III-7) after resolution of macular hemorrhage. D. Case 2, left eye (II-5). E. Case 3, right eye (III-9). F. Case 4, right eye (1-2).
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Cone dystrophy 9 - 1 1 is distinguished by a predominant loss of cone activity best detected by retinal function testing. Electroretinograms show abnormal photopic and flicker responses. The cone por tion of the dark adaptation curve is elevat ed and color vision is abnormal, revealing deutan defects or large accumulations of more nonspecific errors. The electrooculogram is also frequently abnormal, a finding that helps to differentiate cone dystrophy from congenital achromatop sia. A few pedigrees have been examined with progressive atrophy of the macular pigment epithelium 4 ' 5 ; dominantly inher ited, it presents with gradually decreasing vision and a beaten bronze macular lesion similar to Stargardt's disease. No whitish flecks develop in the posterior pole or mid-retinal periphery, however, and cone responses are normal. Subnormal electro-oculograms have been recorded and color vision is defective. Dominant drusen 4 , 5 , 8 usually develop after age 20 as multiple yellowish-white spots in the posterior pole. As the overly ing pigment epithelium and neurosensory retina become increasingly involved, vi sion is reduced. The electroretinogram and dark adaptation test demonstrate a delay in rod recovery; the electrooculogram, a low light/dark ratio. Errors tend to accumulate along the vertical axis on the Farnsworth-Munsell 100-hue test, depending on the degree of macular in volvement. Microscopic sections show a PAS-positive staining material (sialic acid and cerebroside) on the choroidal side of the retinal pigment epithelium, which is presumed to originate from lysozomal autolysis of the retinal pigment epithelial cells. Central areolar choroidal dystro phy 4 ' 5,12 · 13 * 17 is differentiated by progres sive macular atrophy and loss of central vision. The electroretinogram, electrooculogram, and dark adaptation tests
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show normal results, but color vision is usually poor in advanced cases. Atrophy of the choriocapillaries and retinal pig ment epithelium have been observed on fluoresoein angiography and in patholog ic specimens of central areolar choroidal dystrophy lesions, a possible factor in preserving macular function. The pseudoinflammatory macular dys trophy described by Sorsby 3 is a familial macular degeneration that occurs be tween the fourth and fifth decade. Vision is abruptly lost due to a progressive hemorrhagic and exudative macular degenera tion that eventually terminates in a macu lar atrophy resembling central areolar choroidal dystrophy. 4 , 5 The hereditary macular degeneration described first by Lefler, Wadsworth, and Sidbury 1 4 and later by Frank and associ ates 1 5 as "progressive foveal dystrophy" exhibited diverse macular lesions and variable visual impairment. Aminoaciduria was noted in several patients but the significance of this was not estab lished. Retinographs revealed a spectrum of macular lesions that included forms similar to congenital macular colobomas, central areolar choroidal dystrophy, dom inate drusen, and vitelliform dystrophy. It was difficult to differentiate between some of their cases and our own, merely on the basis of ophthalmoscopic appear ance. However, progression of the macu lar atrophy with impairment of vision contrasted sharply with the nohprogressive course in CAPE dystrophy. Vision is little affected and the electrooculogram is markedly subnormal in the butterfly-shaped dystrophy first described in 1970. 18 Because of the unique pattern of macular pigmentation, confusion with other hereditary macular dystrophies would seem unlikely. However, similar pigment migration due to acquired macu lar disease such as central serous retinopathy has been,observed and recorded. 22 Deutman's 7 report of a family with be-
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nign annular concentric macular dystro phy emphasized that poor vision is not a prerequisite for the diagnosis of heredi tary macular dystrophy. These patients exhibited bull's-eye lesions composed of an uninvolved central foveal area sur rounded by a depigmented ring. The ap pearance of these lesions was distinctly different from the lesions in CAPE dys trophy. These two dystrophies also dif fered in that retinal function studies were abnormal in the cases reported by Deutman. However, the significance of the abnormal electroretinogram and electrooculogram, particularly in the proposita, was obscured since this patient had previ ously undergone bilateral retinal detach ment surgery. Ruedemann 2 3 pointed out that the electroretinogram does not return to normal levels after a successful reattachment of the retina. Therefore, it is difficult to determine to what extent the macular dystrophy alone influenced these electrophysiologic findings. We summarized the results of retinal function testing in the recognized domi nant macular dystrophies (Table 2), and those obtained from the family presented in this report (Table 3). The hereditary macular lesions de scribed here must also be differentiated from certain acquired retinal diseases. One defect (Fig. 2, B) could have been
TABLE 3 R E T I N A L F U N C T I O N STUDIES IN CENTRAL AREOLAR PIGMENT EPITHELIAL DYSTROPHY Visual Acuity Case 1*
Color DA Vision
ERG
EOG
N
N
N
A
N N N N N N N
N N N N N N N
N N N N N N N
N N N N N N N
20/200 RE,
LE, RE, LE, Case 3 RE, LE, Case 4 RE, LE, Case 2
20/25 20/25 20/20 20/20 20/20 20/20 20/20 20/20
*This patient's mother reputedly had CAPE dys trophy and normal visual acuity. fN indicates normal; A, abnormal; and DA, dark adaptation.
confused with a postinflammatory lesion, and the macular hemorrhage (Fig. 2, A) could be mistaken for ocular histoplasmosis, juvenile macular degeneration, or hemorrhagic disciform degeneration of the macula. Subretinal neovascularization has been implicated as a predis posing cause of hemorrhage in these conditions, and may have caused one hemorrhage (Fig. 2, A). Distinguishing this lesion from presumed ocular histoplasmosis was not possible based on the ophthalmoscopic appearance by fluorescein angiography. Had this been the only lesion present, our diagnosis might well
TABLE 2 RETINAL FUNCTION STUDIES IN DOMINANT MACULAR DYSTROPHIES*
Dominant Macular Dystrophy Vitelliform Cone dystrophy Progressive macular atrophy Drusen Central choroidal Pseudoinflammatory Progressive foveal dystrophy Butterfly Benign annular concentric
Visual Acuity
ERG
EOG
DA
Color Vision
A A A A A A A N N
N A N N N N N N N/A
A A N/A A N N N A N/A
N A N N N N N N N
A A A A A A N N N
*DA indicates dark adaptation; A, abnormal; N, normal; and N/A, may be normal or abnormal.
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have been histoplasmosis or juvenile disciform macular degeneration. However, similar unique macular lesions in other family members suggested a hereditary rather than an acquired lesion. Also, good visual acuity is rarely recovered after a histoplasmic macular hemorrhage. Al though a striking macular scar remained, visual acuity in one patient's right eye improved to 20/25 (Case 1). Differentia tion of the lesion in the center of the left macula (Case 1) from an old inflammato ry scar was aided chiefly by the negative ocular history, unimpaired visual acuity, and fluorescein angiographie characteris tics. There were different degrees of macular involvement in three successive genera tions of a single family (Fig. 2). It is not uncommon for a dominantly transmitted dystrophy to show increased penetrance and variable expressivity, as in the macu lar alterations of this family. This also occurs in vitelliform dystrophy and domi nant drusen and may account for the variations noted in Lefler's dominant he reditary macular degeneration. SUMMARY
We examined nine members of a family with a unique hereditary macular dystro phy by using stereoscopic color photogra phy, fluorescein angiography, electroretinography, electro-oculography, dark ad aptation, H-R-R color plates, and the Farnsworth-Munsell 100-hue test. The disorder was transmitted as an autosomal-dominant trait with increased penetrance and variable expression. Four of the family members, representing three successive generations, exhibited defects in macular pigmentation ranging from a 1disk diameter excavation to a more subtle central loss of macular pigment. Only one eye with macular hemorrhage had de creased visual acuity; visual acuity in this eye was 20/25 when the hemorrhage re solved. All other retinal function studies
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were normal. The unusual nonprogres sive areolar depigmentation of the central macula together with normal retinal func tions made it impossible to classify this disorder, and indicated a new and unreported dominant macular dystrophy, cen tral areolar pigment epithelial dystrophy. REFERENCES 1. Batten, R. D.: Two brothers with symmetrical disease of the macula, commencing at age 14. Trans. Ophthalmol. Soc. U. K. 17:48, 1897. 2. Stargardt, K.: Ueber familiäre, progressive de generation in der Makulegegard des Auges. Arch. Ophthalmol. 71:534, 1909. 3. Sorsby, A., and Joll-Mason, M. E.: A fundus lesion with unusual features. Br. J. Ophthalmol. 33:67, 1949. 4. Deutman, A. F.: The Hereditary Dystrophies of the Posterior Pole of the Eye. Assen, Van Gorcum, 1971, pp. 1-47. 5. : Macular dystrophies. In Goldberg, M. (ed.): Genetic and Metabolic Eye Disease. Boston, Little Brown and Co., 1974, p. 367. 6. : Electro-oculography in families with vitelliform dystrophy of the fovea. Arch. Ophthal mol. 81:304, 1969. 7. : Benign concentric annular macular dystrophy. Am. J. Ophthalmol. 78:384, 1974. 8. Deutman, A. F., and Jansen, L. M. A. A.: Dominantly inherited drusen of Bruch's membrane. Br. J. Ophthalmol. 54:373, 1970. 9. Krill, A. E., and Deutman, A. F.: The various categories of juvenile macular degeneration. Trans. Am. Ophthalmol. Soc. 70:562, 1971. 10. : Dominant macular degenerations. The cone dystrophies. Am. J. Ophthalmol. 73:342, 1972. 11. Krill, A. E., Deutman, A. F., and Fishman, M.: The cone degenerations. Doc. Ophthalmol. 35:1, 1973. 12. Krill, A. E., and Archer, D.: Classification of the choroidal atrophies. Am. J. Ophthalmol. 72:562, 1971. 13. Sorsby, A., and Crick, R. P.: Central areolar choroidal sclerosis. Br. J. Ophthalmol. 37:129,1953. 14. Lefler, W. H., Wadsworth, J. A. C , and Sid bury, J. B., Jr.: Hereditary macular degeneration and aminoaciduria. Am. J. Ophthalmol. 71:224, 1971. 15. Frank, R. H., Landers, M. D., Williams, R. J., and Sidbury, J. B.: A new dominant progressive foveal dystrophy. Am. J. Ophthalmol. 78:903,1974. 16. Falls, H. F.: A classification and clinical de scription of hereditary macular lesions. Trans. Am. Acad. Ophthalmol. Otolaryngol. 70:1034, 1966. 17. Carr, R. E.: Central areolar choroidal dystro phy. Arch. Ophthalmol. 73:32, 1965. 18. Deutman, A. F., Von Blommestein, J., Henkes, H. E., Waardenburg, P. J., and Van Driest,
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E. S.: Butterfly-shaped pigment dystrophy of the fovea. Arch. Ophthalmol. 83:558, 1970. 19. Rabin, A. R., and Berson, E. L.: A full-field system for clinical electroretinography. Arch. Ophthalmol. 92:59, 1974. 20. Birndorff, L. A., and Dawson, W. W.: A nor mal electro-oculogram in a patient with a typical vitelliform macular lesion. Invest. Ophthalmol. 12:830, 1973. 21. Fine, S. L., and Yoder, F. E.: Best's vitelliruptive macular dystrophy with normal electro-
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oculogram findings: report of a kindred. Presented at the Association for Research in Vision and Oph thalmology Spring Meeting, Sarasota, Florida, April 25, 1974. 22. Gass, J. D.: Stereoscopic Atlas of Macular Diseases. St. Louis, C. V. Mosby Company, 1970, p. 25. 23. Ruedmann, A. D., Jr.: Retinal detachment. The electroretinogram in the fellow eye. Trans. Am. Acad. Ophthalmol. Otolaryngol. 69:51, 1965.
OPHTHALMIC MINIATURE
All this Indian turquoise jewelry seen now brings to mind some of the superstitions that have arisen about turquoise. The Indians thought it to bring good luck to those who handled or owned it. In Germany, the old saying was that the turquoise when given to a lover would retain its color as long as the lover was true. In Afghanistan, when a turquoise ring was dipped in water and applied to the eyes, it would cure cataracts. And in Arabia and Persia, the stone was believed to cure night blindness, dispel fear, and protect the wearer from drowning, lightning, and snake bites. In Russia, soldiers were advised to wear the stone to protect them from fatal wounds in battle. Through the ages that stone has been recommend ed as a cure for melancholy, swelling, dyspepsia, insanity, and ulcers. Almanac, The Chicago Tribune May 16, 1976
N E L S O N GURNEY,
M.D.,
J. G R A H A M D O B B I E , M.D., AND E A R L C H O R O M O K O S
Chicago, Illinois
At the turn of the century, Batten 1 and Stargardt 2 introduced the subject of fa milial disease of the macula. Since that time several hereditary macular dystro phies have been described and record ed. 3 - 1 8 Table 1 categorizes some of the more widely recognized dystrophies ac cording to mode of transmission. Early studies emphasized genetic and ophthalmoscopic characteristics. More recent studies have attempted to examine struc tural and functional déficiences by means of fluorescein angiography and retinal function analysis. Most of these dystrophies represent discrete nosologie entities. Variations do occur within these groups (for example, vitelliform), but these are now well recog nized. A few are less well defined (for example, Sorsby's pseudoinflammatory macular dystrophy) and may be easily confused with other hereditary or ac quired macular defects. Almost all of the dominant macular hereditary dystrophies are associated with visual impairment or abnormal retinal function studies at some stage of their development. Deutman 7 de scribed a new dominant macular dystro phy characterized by good vision and a benign course in which retinal function studies were abnormal. In our study, good visual acuity was generally preserved and retinal function studies were normal. There was no pro gression of the lesion. The macular leFrom the Northwestern University Medical School, Department of Ophthalmology, Chicago, Illinois. Presented at the American Ophthalmology Socie ty Meeting, Hot Springs, Virginia, May 30, 1975. Reprint requests to Carl L. Fetkenhour, M.D., Northwestern Memorial Hospital, 707 N. Fairbanks Court, Chicago, IL 60611.
sions were central, depigmented, sharply demarcated, and involved primarily the pigment epithelium. We are, therefore, calling this dystrophy central areolar pig ment epithelial (CAPE) dystrophy. M A T E R I A L AND M E T H O D S
We examined nine members of one family (Fig. 1), using stereoscopic color photography and fluorescein angiogra phy, electro-oculography, dark adapta tion, H-R-R color plates, and the Farnsworth-Munsell 100-hue test. Electroretinography was performed with a ganzfeld stimulator and blue, red, and white light stimuli. 1 9 Single urine sam ples were obtained from all affected fami ly members for Chromatographie amino acid analysis. CASE REPORTS
Case 1—The proband, a 13-year-old white boy (III-7), had sudden loss of visual acuity in the right eye. He denied previous ocular problems. Corrected visual acuity was R.E.: 20/200, and L.E.: 20/25. A well-circumscribed subretinal hemorrhage and edema were noted in the right macula (Fig. 1, A). The left macula revealed a 1-disk diameter zone of pigment epithelial atrophy with an excavation into the choroid (Fig. 2, B). Optic disks, retinal vessels, and peripheral retinas were normal. Fluorescein angiography of the right eye demonstrated a central macular leakage of dye surrounded by hemorrhage (Fig. 3, A) and in the left eye, hyperfluorescent show-through (Fig. 3, B) corresponding to the de pigmented macula. Electroretinography, electrooculography, and dark adaptation were normal in each eye. Color vision abnormalities in the right eye consisted of several missed H-R-R color plates and more than 600 errors arranged in a nonspecific pattern on the Farnsworth-Munsell 100-hue test. Color vision was normal in the left eye. The urine amino acid analysis was normal. Sixteen months after its onset, the macular hemorrhage resolved and visual acuity was 20/25 (Figs. 2, C and 3, C). This boy's mother (II-4) was killed at age 21 in an automobile accident. Family members reported that she had no visual impairment, but "retinal scars" had been detected in both eyes by previous exami ners.
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TABLE 1 MACULAR DYSTROPHIES ACCORDING TO MODE OF TRANSMISSION
Dominant
Recessive
Vitelliform Cone dystrophy Progressive macular atrophy Drusen Central choroidal Pseudoinflammatory Progressive foveal dystrophy Butterfly Benign annular concentric
Fundus flavimaculatus Reticular Central retinitis pigmentosa Grouped pigmentation
Case 2—A 32-year-old woman, the proband's ma ternal aunt (II-5), had visual acuity of 20/20 in both eyes and no ocular complaints. Macular depigmentation was noted in both eyes (Fig. 2, D). Otherwise, the retinal vessels and optic disk were normal. Fluorescein angiography revealed bilateral hyperfluorescence in each macula (Fig. 3, D). Electroretinography, electro-oculography, dark adaptation, and color vision were normal. Case 3—A 7-year-old girl, the maternal cousin (III-9) of the proband, was asymptomatic with visu al acuity of 20/20 in both eyes. She demonstrated similar bilateral central pigment epithelial defects (Fig. 2, E). The fundi were otherwise normal. Fluo rescein angiography again revealed bright showthrough of the underlying choroidal fluorescence (Fig. 3, E). All retinal function studies were normal, and the urine amino acid analysis was normal. Case 4—A 60-year-old man, the proband's mater nal grandfather (1-2), had no ocular complaints. Visual acuity was 20/20 in both eyes. Macular depigmentation (Fig. 2, F) was not as striking as in the other affected family members, but fluorescein angi ography (Fig. 3, F) revealed a similar hyperfluorescent show-through pattern. The urine amino acid analysis was normal.
o 3
4
X-Chromosome Linked
DISCUSSION
The clinical course of this pigment epi thelial dystrophy was characterized by childhood onset, good visual acuity, and nonprogression. With one exception these patients were asymptomatic. Normal reti nal function studies corroborated the be nign nature of the dystrophy and ruled out a diffuse retinal degeneration. No other dominant hereditary macular dys trophy has these characteristics. Vitelliform degeneration may present as an intact (vitelline) or "scrambled" (vitelliruptive) egg yolk lesion, or macular hemorrhage. Although visual deteriora tion is the rule and the electro-oculogram is classically decreased, recent studies 2 0 , 2 1 have disclosed normal electro-oculograms in patients with typical vitelliform lesions. However, we considered this a rare possibility.
O
5
.
7
6
Juvenile retinoschisis
Π
UNAFFECTED
W H
AFFECTED
©
REPUTEDLY AFFECTED PROBAND
9 10 8 X Fig. 1 (Fetkenhour and associates). Pedigree of family with central areolar pigment epithelial dystrophy; circles represent females and squares, males.
Α. Case 1, right eye (III-7).
C. Case 1, right eye (111-7) after resolution of macular hemorrhage.
E. Case 3, right eye (III-9).
B. Case 1, left eye (III-7).
D. Case 2, left eye (II-5).
F . Case 4, right eye (1-2).
Fig. 2 (Fetkenhour and associates).
Fig. 3 (Fetkenhour and associates). Fluorescein angiography. Α. Case 1, right eye (III-7). Β. Case 1, left eye (III-7). C. Case 1, right eye (III-7) after resolution of macular hemorrhage. D. Case 2, left eye (II-5). E. Case 3, right eye (III-9). F. Case 4, right eye (1-2).
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Cone dystrophy 9 - 1 1 is distinguished by a predominant loss of cone activity best detected by retinal function testing. Electroretinograms show abnormal photopic and flicker responses. The cone por tion of the dark adaptation curve is elevat ed and color vision is abnormal, revealing deutan defects or large accumulations of more nonspecific errors. The electrooculogram is also frequently abnormal, a finding that helps to differentiate cone dystrophy from congenital achromatop sia. A few pedigrees have been examined with progressive atrophy of the macular pigment epithelium 4 ' 5 ; dominantly inher ited, it presents with gradually decreasing vision and a beaten bronze macular lesion similar to Stargardt's disease. No whitish flecks develop in the posterior pole or mid-retinal periphery, however, and cone responses are normal. Subnormal electro-oculograms have been recorded and color vision is defective. Dominant drusen 4 , 5 , 8 usually develop after age 20 as multiple yellowish-white spots in the posterior pole. As the overly ing pigment epithelium and neurosensory retina become increasingly involved, vi sion is reduced. The electroretinogram and dark adaptation test demonstrate a delay in rod recovery; the electrooculogram, a low light/dark ratio. Errors tend to accumulate along the vertical axis on the Farnsworth-Munsell 100-hue test, depending on the degree of macular in volvement. Microscopic sections show a PAS-positive staining material (sialic acid and cerebroside) on the choroidal side of the retinal pigment epithelium, which is presumed to originate from lysozomal autolysis of the retinal pigment epithelial cells. Central areolar choroidal dystro phy 4 ' 5,12 · 13 * 17 is differentiated by progres sive macular atrophy and loss of central vision. The electroretinogram, electrooculogram, and dark adaptation tests
JUNE, 1976
show normal results, but color vision is usually poor in advanced cases. Atrophy of the choriocapillaries and retinal pig ment epithelium have been observed on fluoresoein angiography and in patholog ic specimens of central areolar choroidal dystrophy lesions, a possible factor in preserving macular function. The pseudoinflammatory macular dys trophy described by Sorsby 3 is a familial macular degeneration that occurs be tween the fourth and fifth decade. Vision is abruptly lost due to a progressive hemorrhagic and exudative macular degenera tion that eventually terminates in a macu lar atrophy resembling central areolar choroidal dystrophy. 4 , 5 The hereditary macular degeneration described first by Lefler, Wadsworth, and Sidbury 1 4 and later by Frank and associ ates 1 5 as "progressive foveal dystrophy" exhibited diverse macular lesions and variable visual impairment. Aminoaciduria was noted in several patients but the significance of this was not estab lished. Retinographs revealed a spectrum of macular lesions that included forms similar to congenital macular colobomas, central areolar choroidal dystrophy, dom inate drusen, and vitelliform dystrophy. It was difficult to differentiate between some of their cases and our own, merely on the basis of ophthalmoscopic appear ance. However, progression of the macu lar atrophy with impairment of vision contrasted sharply with the nohprogressive course in CAPE dystrophy. Vision is little affected and the electrooculogram is markedly subnormal in the butterfly-shaped dystrophy first described in 1970. 18 Because of the unique pattern of macular pigmentation, confusion with other hereditary macular dystrophies would seem unlikely. However, similar pigment migration due to acquired macu lar disease such as central serous retinopathy has been,observed and recorded. 22 Deutman's 7 report of a family with be-
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PIGMENT EPITHELIAL DYSTROPHY
nign annular concentric macular dystro phy emphasized that poor vision is not a prerequisite for the diagnosis of heredi tary macular dystrophy. These patients exhibited bull's-eye lesions composed of an uninvolved central foveal area sur rounded by a depigmented ring. The ap pearance of these lesions was distinctly different from the lesions in CAPE dys trophy. These two dystrophies also dif fered in that retinal function studies were abnormal in the cases reported by Deutman. However, the significance of the abnormal electroretinogram and electrooculogram, particularly in the proposita, was obscured since this patient had previ ously undergone bilateral retinal detach ment surgery. Ruedemann 2 3 pointed out that the electroretinogram does not return to normal levels after a successful reattachment of the retina. Therefore, it is difficult to determine to what extent the macular dystrophy alone influenced these electrophysiologic findings. We summarized the results of retinal function testing in the recognized domi nant macular dystrophies (Table 2), and those obtained from the family presented in this report (Table 3). The hereditary macular lesions de scribed here must also be differentiated from certain acquired retinal diseases. One defect (Fig. 2, B) could have been
TABLE 3 R E T I N A L F U N C T I O N STUDIES IN CENTRAL AREOLAR PIGMENT EPITHELIAL DYSTROPHY Visual Acuity Case 1*
Color DA Vision
ERG
EOG
N
N
N
A
N N N N N N N
N N N N N N N
N N N N N N N
N N N N N N N
20/200 RE,
LE, RE, LE, Case 3 RE, LE, Case 4 RE, LE, Case 2
20/25 20/25 20/20 20/20 20/20 20/20 20/20 20/20
*This patient's mother reputedly had CAPE dys trophy and normal visual acuity. fN indicates normal; A, abnormal; and DA, dark adaptation.
confused with a postinflammatory lesion, and the macular hemorrhage (Fig. 2, A) could be mistaken for ocular histoplasmosis, juvenile macular degeneration, or hemorrhagic disciform degeneration of the macula. Subretinal neovascularization has been implicated as a predis posing cause of hemorrhage in these conditions, and may have caused one hemorrhage (Fig. 2, A). Distinguishing this lesion from presumed ocular histoplasmosis was not possible based on the ophthalmoscopic appearance by fluorescein angiography. Had this been the only lesion present, our diagnosis might well
TABLE 2 RETINAL FUNCTION STUDIES IN DOMINANT MACULAR DYSTROPHIES*
Dominant Macular Dystrophy Vitelliform Cone dystrophy Progressive macular atrophy Drusen Central choroidal Pseudoinflammatory Progressive foveal dystrophy Butterfly Benign annular concentric
Visual Acuity
ERG
EOG
DA
Color Vision
A A A A A A A N N
N A N N N N N N N/A
A A N/A A N N N A N/A
N A N N N N N N N
A A A A A A N N N
*DA indicates dark adaptation; A, abnormal; N, normal; and N/A, may be normal or abnormal.
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have been histoplasmosis or juvenile disciform macular degeneration. However, similar unique macular lesions in other family members suggested a hereditary rather than an acquired lesion. Also, good visual acuity is rarely recovered after a histoplasmic macular hemorrhage. Al though a striking macular scar remained, visual acuity in one patient's right eye improved to 20/25 (Case 1). Differentia tion of the lesion in the center of the left macula (Case 1) from an old inflammato ry scar was aided chiefly by the negative ocular history, unimpaired visual acuity, and fluorescein angiographie characteris tics. There were different degrees of macular involvement in three successive genera tions of a single family (Fig. 2). It is not uncommon for a dominantly transmitted dystrophy to show increased penetrance and variable expressivity, as in the macu lar alterations of this family. This also occurs in vitelliform dystrophy and domi nant drusen and may account for the variations noted in Lefler's dominant he reditary macular degeneration. SUMMARY
We examined nine members of a family with a unique hereditary macular dystro phy by using stereoscopic color photogra phy, fluorescein angiography, electroretinography, electro-oculography, dark ad aptation, H-R-R color plates, and the Farnsworth-Munsell 100-hue test. The disorder was transmitted as an autosomal-dominant trait with increased penetrance and variable expression. Four of the family members, representing three successive generations, exhibited defects in macular pigmentation ranging from a 1disk diameter excavation to a more subtle central loss of macular pigment. Only one eye with macular hemorrhage had de creased visual acuity; visual acuity in this eye was 20/25 when the hemorrhage re solved. All other retinal function studies
JUNE, 1976
were normal. The unusual nonprogres sive areolar depigmentation of the central macula together with normal retinal func tions made it impossible to classify this disorder, and indicated a new and unreported dominant macular dystrophy, cen tral areolar pigment epithelial dystrophy. REFERENCES 1. Batten, R. D.: Two brothers with symmetrical disease of the macula, commencing at age 14. Trans. Ophthalmol. Soc. U. K. 17:48, 1897. 2. Stargardt, K.: Ueber familiäre, progressive de generation in der Makulegegard des Auges. Arch. Ophthalmol. 71:534, 1909. 3. Sorsby, A., and Joll-Mason, M. E.: A fundus lesion with unusual features. Br. J. Ophthalmol. 33:67, 1949. 4. Deutman, A. F.: The Hereditary Dystrophies of the Posterior Pole of the Eye. Assen, Van Gorcum, 1971, pp. 1-47. 5. : Macular dystrophies. In Goldberg, M. (ed.): Genetic and Metabolic Eye Disease. Boston, Little Brown and Co., 1974, p. 367. 6. : Electro-oculography in families with vitelliform dystrophy of the fovea. Arch. Ophthal mol. 81:304, 1969. 7. : Benign concentric annular macular dystrophy. Am. J. Ophthalmol. 78:384, 1974. 8. Deutman, A. F., and Jansen, L. M. A. A.: Dominantly inherited drusen of Bruch's membrane. Br. J. Ophthalmol. 54:373, 1970. 9. Krill, A. E., and Deutman, A. F.: The various categories of juvenile macular degeneration. Trans. Am. Ophthalmol. Soc. 70:562, 1971. 10. : Dominant macular degenerations. The cone dystrophies. Am. J. Ophthalmol. 73:342, 1972. 11. Krill, A. E., Deutman, A. F., and Fishman, M.: The cone degenerations. Doc. Ophthalmol. 35:1, 1973. 12. Krill, A. E., and Archer, D.: Classification of the choroidal atrophies. Am. J. Ophthalmol. 72:562, 1971. 13. Sorsby, A., and Crick, R. P.: Central areolar choroidal sclerosis. Br. J. Ophthalmol. 37:129,1953. 14. Lefler, W. H., Wadsworth, J. A. C , and Sid bury, J. B., Jr.: Hereditary macular degeneration and aminoaciduria. Am. J. Ophthalmol. 71:224, 1971. 15. Frank, R. H., Landers, M. D., Williams, R. J., and Sidbury, J. B.: A new dominant progressive foveal dystrophy. Am. J. Ophthalmol. 78:903,1974. 16. Falls, H. F.: A classification and clinical de scription of hereditary macular lesions. Trans. Am. Acad. Ophthalmol. Otolaryngol. 70:1034, 1966. 17. Carr, R. E.: Central areolar choroidal dystro phy. Arch. Ophthalmol. 73:32, 1965. 18. Deutman, A. F., Von Blommestein, J., Henkes, H. E., Waardenburg, P. J., and Van Driest,
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E. S.: Butterfly-shaped pigment dystrophy of the fovea. Arch. Ophthalmol. 83:558, 1970. 19. Rabin, A. R., and Berson, E. L.: A full-field system for clinical electroretinography. Arch. Ophthalmol. 92:59, 1974. 20. Birndorff, L. A., and Dawson, W. W.: A nor mal electro-oculogram in a patient with a typical vitelliform macular lesion. Invest. Ophthalmol. 12:830, 1973. 21. Fine, S. L., and Yoder, F. E.: Best's vitelliruptive macular dystrophy with normal electro-
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oculogram findings: report of a kindred. Presented at the Association for Research in Vision and Oph thalmology Spring Meeting, Sarasota, Florida, April 25, 1974. 22. Gass, J. D.: Stereoscopic Atlas of Macular Diseases. St. Louis, C. V. Mosby Company, 1970, p. 25. 23. Ruedmann, A. D., Jr.: Retinal detachment. The electroretinogram in the fellow eye. Trans. Am. Acad. Ophthalmol. Otolaryngol. 69:51, 1965.
OPHTHALMIC MINIATURE
All this Indian turquoise jewelry seen now brings to mind some of the superstitions that have arisen about turquoise. The Indians thought it to bring good luck to those who handled or owned it. In Germany, the old saying was that the turquoise when given to a lover would retain its color as long as the lover was true. In Afghanistan, when a turquoise ring was dipped in water and applied to the eyes, it would cure cataracts. And in Arabia and Persia, the stone was believed to cure night blindness, dispel fear, and protect the wearer from drowning, lightning, and snake bites. In Russia, soldiers were advised to wear the stone to protect them from fatal wounds in battle. Through the ages that stone has been recommend ed as a cure for melancholy, swelling, dyspepsia, insanity, and ulcers. Almanac, The Chicago Tribune May 16, 1976