Embed Size (px)
Citation preview
Evolution of Benign Concentric Annular MacularDystrophy
P. R. van den Biesen, M.D., A. F. Deutman, M.D., and A. J. L. G. Pinckers, M.D.
In 1974, Deutman described a family with anautosomal dominantly inherited macular dystrophythat he termed "benign concentric annular macular(bulls-eye) dystrophy." Ten years later, we performed a follow-up examination. Some patientscomplained of deterioration of visual acuity, nightvision, arid color vision. The macular dystrophy hadprogressed. The fundus periphery was more involved and in two patients there were bonecorpuscle-like pigmentations. Electrophysiologicexamination showed increased photoreceptor dysfunction with equal involvement of the rod andcone system. The patients had an acquired type IIIblue-yellow color vision defect with pseudoprotanomaly.
IN 1974, DEUTMAN! described a family with a macular dystrophy showing a depigmented ring aroundan intact central area. There was no history of chloroquine ingestion and there were no symptoms typicalof cone dystrophy. The visual acuity was only minimally affected. Deutman termed this autosomaldominantly inherited macular disorder "benign concentric annular macular (bull's-eye) dystrophy." Tenyears after the initial examination, we performed afollow-up examination of three of the originally described patients. In addition, three other familymembers are presented herein (Fig. 1). The dystrophy seemed to have developed into a more diffusepigmentary retinopathy with functional characteristics of a cone-rod dystrophy.
Our study of the patients included routine evaluation, Goldmann kinetic perimetry, electroretinography, electro-oculography, fluorescein angiography, and elaborate color-vision testing (Tablej.P"
From the Department of Ophthalmology, University of Nijmegen. The Netherlands.
Reprint requests to P. R. van den Biesen, M.D., Department ofOphthalmology, Radboudhospital, Philips van Leydenlaan 15,6500 HB Nijmegen, The Netherlands.
Case Reports
Case 1The 28-year-old proband (who had suffered bilater
al retinal detachments before the first examination in1974, when she was presented as Case 1 by Deutman') had noticed marked deterioration of visualacuity, night vision, and color vision.
Her visual acuity was R.E.: 20/60 with 5+2 C-2axis 180; and L.E.: 20/40 with 5+2.25 C-1.75 axis 20.There was a bull's-eye maculopathy, waxy opticatrophy, peripapillary atrophy, attenuated retinalarterioles, and peripheral bone-spicule pigmentation (Fig. 2). There were signs of detachmentsurgery with scleral resection. The fluorescein angiogram of the macula showed pericentral hyperfluorescence that indicated dystrophy of the pigmentepithelium and choriocapillaris (Fig. 3). There was ageneralized contraction of the Goldmann visualfields with an incomplete ring scotoma and superiorconstriction. The electroretinogram in both eyes wasphotopically and scotopically unrecordable. Thelight-peak/dark-trough ratio was 1.00 in the right eyeand 1.00 in the left eye. The dark adaptation curvewas 1.5 log units elevated. Color vision showed anacquired type I red-green defect.
Case 2The brother of the proband (Case 2 in 1974) (age, 26
years) had no visual complaints.His visual acuity was R.E.: 20/15 uncorrected, and
L.E.: 20/15 uncorrected. There was a bull's-eye maculopathy, attenuated arterioles, peripapillary atrophy, and some faint granular pigmentary disturbance in the periphery (Fig. 4). Fluoresceinangiography of the macula showed a pericentraldystrophy of pigment epithelium (Fig. 5). The Goldmann visual fields were slightly contracted. Theelectroretinogram disclosed a slightly decreasedcone and rod function without a prevalence of either.The light-peak/dark-trough ratio was normal; R.E.:2.00, and L.E.: 1.75. Dark adaptation was undisturbed.
©AMERICAN JOURNAL OF OPHTHALMOLOGY 100:73--78, JULY, 1985 73
74
II
III
IV
V
AMERICAN JOURNAL OF OPHTHALMOLOGY July, 1985
Fig. 1 (Van den Biesen, Deutman, andPinckers). Family pedigree.
Case 3The mother of the proband (Case 3 in 1974) (age, 54
years) complained of decreased visual acuity, disturbed color vision, night blindness, and some photophobia.
Her visual acuity was R.E.: 20/40 with 5+6.25C-0.5 x 80; and L.E.: 20/25 with 5+6.75 C-0.5 x135. The fundus showed a bull's-eye maculopathy,waxy optic atrophy, peripapillary atrophy, attenuated arterioles, and granular pigment disturbance inthe periphery (Fig. 6). Fluorescein angiography ofthe macula demonstrated pericentral dystrophy ofpigment epithelium and choriocapillaris, in the righteye more than in the left eye (Figs. 7 and 8). TheGoldmann visual fields showed a deep generalizedcontraction and a relative central scotoma in the right
eye that was more pronounced than in the left eye.The electroretinogram showed unrecordable rodfunction and decreased cone function. The lightpeak/dark-trough ratio was R.E.: 1.11, and L.E.:0.97. The dark-adaptation curve was 1 log unit elevated.
Case 4The grandmother of the proband (Case 4 in 1974)
did not undergo a second examination.
Case 5The 50-year-old aunt of the proband had com
plained of some photophobia, disturbed color vision,and decreased night vision.
Her visual acuity was R.E.: 20/25 with 5+0.5
TABLESUMMARY OF CLINICAL DATA
ELECTRO-
EXAMINATION VISUAL OCULOG-
ACUITY DARK·ADAPTATION ELECTRORETINOGRAPHY RAPHYPATIENT AGE ELEVATION
NO. YEAR (YRS) R.E. L.E. COLOR VISION (LOG UNITS) SCOTOPIC PHOTOPIC R.E. L.E.
1974 18 20/60 20/25 Blue-yellow defect; diminished Subnormal Subnormal 1.00 1.00red sensitivity
1984 28 20/60 20/40 Red-green defect; diminished 1.5 Unrecordable Unrecordable 1.00 1.00red sensitivity
2 1974 16 20/20 20/20 Diminished red sensitivity Normal Normal Subnormal 2.14 2.361984 26 20115 20115 Norma! Subnormal Subnormal 2.00 1.75
3 1974 44 20/25 20/25 Blue-yellow defect; diminished 1.0 Subnormal Subnormal 1.87 1.91red sensitivity
1984 54 20/40 20/25 1.0 Unrecordable Subnormal 1.11 0.974 1971 70 20/20 20/25 Blue-yellow defect Normal Normal 1.74 1.655 1984 50 20/25 20/20 Blue-yellow defect; diminished 0.5 Subnormal Subnormal 1.12 1.00
red sensitivity
6 1984 45 20/25 20/25 0.5 Subnormal Subnormal 1.50 1.707 1984 24 20/25 20/25 Diminished red sensitivity 0.5 Subnormal Subnormal 1.22 1.27
Vol. 100, No. 1 Annular Macular Dystrophy 75
Fig. 2 (Van den Biesen, Deutman, and Pinckers). Rightmacula of Patient 1. Visual acuity: 20/60 (red-free photograph).
C-0.25xI70; and L.E.: 20/20 with 5+0.25 C-0.5xI0.There was a bull's-eye maculopathy, waxy opticatrophy, peripapillary atrophy, attenuated arterioles, and bone-spicule pigmentation (Fig. 9). Thefluorescein angiogram of the macula showed pericentral pigment epithelial dystrophy. The Goldmannvisual fields demonstrated a generalized contraction,
Fig. 4 (Van den Biesen, Deutman, and Pinckers). Leftmacula of Patient 2. Visual acuity: 20/15 (red-free photograph) '.
Fig. 3 (Van den Biesen, Deutman, and Pinckers). Fluorescein angiogram of right macula in Patient 1.
an enlarged blind spot, and superior construction.The electroretinogram showed a subnormal cone androd function. The light-peak/dark-trough ratio wasR.E.: 1.12, and L.E.; 1.00. The dark-adaptation curvewas 0.5 log unit elevated. Color-vision testing disclosed an acquired type III blue-yellow defect withpseudoprotanomaly.
Fig. 5 (Van den Biesen, Deutman, and Pinckers). Fluorescein angiogram of left macula of Patient 2 showing dystrophy of pigment epithelium.
76 AMERICAN JOURNAL OF OPHTHALMOLOGY July, 1985
Fig. 6 (Van den Biesen, Deutman, and Pinckers). Rightmacula of Patient 3. Visual acuity: 20/40 (red-free photograph).
Case 6The 45-year-old aunt of the proband had noticed a
deterioration of color vision and decreased nightvision.
Her visual acuity was R.E.: 20/25 with 5+2.75C-0.5 x 30; and L.E.: 20/25 with 5+3.75 C-1.25 x175. The fundus showed a bull's-eye maculopathy,
Fig. 8 (Van den Biesen, Deutman, and Pinckers). Latephase fluorescein angiogram of Patient 3.
Fig. 7 (Van den Biesen, Deutman, and Pinckers). Earlyphase fluorescein angiogram of Patient 3 showing dystrophy of retinal pigment epithelium and choriocapillaris.
normal optic disks, attenuated arterioles, and peripheral granular pigment disturbance. Fluoresceinangiography demonstrated pericentral dystrophy ofthe pigment epithelium. The Goldmann visual fieldswere generally depressed. The electroretinogramshowed slightly decreased for both rod and conefunction. The light-peak/dark-trough ratio was R.E.:
Fig. 9 (Van den Biesen, Deutman, and Pinckers). Periphery in Patient 5 showing bone-spicule pigmentation.
Vol. 100, No.1 Annular Macular Dystrophy 77
1.50 and L.E.: 1.7. The dark-adaptation curve was 0.5log unit elevated.
Case 7The 24-year-old daughter of Patient 5 had com
plaints of decreased night vision.Her visual acuity was R.E.: 20/25 with 5+2.75
C-1.5x60; and L.E.: 20/25 with 5+2.25 C-0.5x90.There were pericentral pigment alterations, waxyoptic atrophy, peripapillary atrophy, slight attenuated arterioles, md some paravenous pigment clumping in the periphery. The fluorescein angiogramshowed a pericentral pigment epithelial dystrophy.The Goldmann visual fields disclosed deep generalized contraction. The electroretinogram was subnormal for cone and rod function. The light-peak/darktrough ratio was R.E.: 1.22 and L.E.: 1.27. Thedark-adaptation curve was 0.5 log unit elevated.Color-vision testing showed pseudoprotanomaly.
Discussion
This family showed a benign retinal dystrophywith what is probably an autosomal-dominant inheritance pattern. Inheritance from father to son couldnot be demonstrated, but three successive generations were affected. The degree of affect differedgreatly among the family members, which is notsurprising, because variability in expression is generally a hallmark of autosomal-dominant disease.The grandmother of the proband had no visual complaints at all. The proband noticed deterioration ofvisual acuity and color and night vision. The fundusdisorders ranged from macular-pigment alterationsto bull's-eye maculopathy, and from minimalperipheral-pigment disturbance to a full-grown pigmentary dystrophy with clumps of pigment andbone corpuscles. Fluorescein angiography showeddystrophy of the perifoveal pigment epithelium and,in the more severely affected patients, a dystrophy ofthe choriocapillaris. On electroretinography therewas no clear predominance of cone or rod dysfunction. In one patient, both the cone and rod systemswere unrecordable. The dark-adaptation curveended on a normal or a moderately elevated level.There were acquired blue-yellow color vision defectswith pseudoprotanomaly. Because of the naturaldevelopment or the function-test results, it is difficult to differentiate this disease from autosomaldominant retinitis pigmentosa. However, photopicfunctions are clearly affected early, indicating acone-rod, mixed, or diffuse tapetoretinal dystrophy.Deutman" stated that pigmentary retinal dystrophiesin which rods and cones are equally affected (mixed
dystrophy) stand out clearly from those dystrophiesin which the rods are affected primarily and predominantly (retinitis pigmentosa), and from those dystrophies in which the cones are affected primarilyand predominantly (cone dystrophy).
Massof and Finkelstein" divided autosomal-dominant retinitis pigmentosa on the basis of psychophysical measures of rod and cone sensitivity loss intwo types. Type I was characterized by an earlydiffuse loss of rod sensitivity with a later loss of conesensitivity and by the childhood onset of blindness.Type II was characterized by a combined loss of rodand cone sensitivity with the adult onset of nightblindness. Arden and colleagues" divided patientswith autosomal-dominant retinitis pigmentosa intotwo groups on the basis of extended electroretinographic testing. Group A consisted of patients withunrecordable rod B-waves and group B consisted ofpatients with residual rod function. Arden and as soelates" suggested that cells other than photoreceptorsare primarily affected in some cases of group B.
Pinckers, Cruysberg, and Aan de Kerk" made afunctional classification of the main types of bull'seye maculopathy. They described a type of bull's-eyemaculopathy and presumed the primary site of disease to be in the retinal pigment epithelium orchoriocapillaris, with a nonselective degeneration ofboth cones and rods as a consequence. In theirdepth-localization theory, Pinckers, Cruysberg, andAan de Kerk" explained the blue-yellow color-visiondefect with decreased red sensitivity as result ofreceptor misalignment with preserved central fixation secondary to a process in the retinal pigmentepithelium.
In 1972, Deutman had already indicated the resemblance of the fundus disorders in this family toacquired chloroquine retinopathy. It is known thatchloroquine is selectively accumulated in the choroidand pigment epithelium." This family was originallydescribed as suffering from a characteristic maculardystrophy, albeit with some peripheral retinal abnormalities and decreased, diffuse results of retinalfunction testing. Follow-up examination showed aclear evolution into an autosomal-dominant inherited pigmentary dystrophy with variable expression inwhich both the cone and rod systems are almostequally affected. 10
The most constant and predominant ophthalmoscopic finding was the concentric annular maculardystrophy. This bull's-eye-like lesion may also beseen in cone dystrophy and in dominant retinitispigmentosa. As for pigmentary dystrophy, subdivision into the type II of Massof and Finkelstein" andthe type B of Arden and colleagues? is possible.Regarding the macular changes, classification as aretinal pigment-epithelial type of bull's-eye maculop-
78 AMERICAN JOURNAL OF OPHTHALMOLOGY July, 1985
athy identified by Pinckers, Cruysberg, and Aan deKerk8 is also possible. Because of the nonselectivedysfunction of cones and rods, it is tempting tolocate the primary defect of this disorder in theretinal pigment epithelium.
References
1. Deutrnan, A. F.: Benign concentric annular maculardystrophy. Am. J. Ophthalmo!. 78:384, 1974.
2. Pinckers, A.: Clinical electrooculography. Acta Ophthalmo!' 57:623, 1979.
3. Pinckers, A.: Color vision and age. Ophthalmologica181:23, 1980.
4. Thijssen, J. M., Pinckers, A., and Otto, A. J.: A multipurpose system for ophthalmic electrodiagnosis. Ophthalmologica 168:308, 1974.
5. Deutman, A. F.: The Hereditary Dystrophies of thePosterior Pole of the Eye. Assert, van Gorcum and Camp,1971, p. 429.
6. Massof, R. W., and Finkelstein, D.: Two forms ofautosomal dominant primary retinitis pigmentosa. Doc.Ophthalmo!. 51:289, 1981.
7. Arden, C. B., Carter, R. M., Hogg, C. R., Powell,D. J., Ernst, W. J., Clover, G. M., Lyness, A. 1., and Quinlan, M. P.: Rod and cone activity in patients with dominantly inherited retinitis pigmentosa. Comparison betweenpsycho-physical and electroretinographic measurements.Br. J. Ophthalmo!. 67:405, 1983.
8. Pinckers, A., Cruysberg, J. R. M., and Aan de Kerk,A. 1.: Main types of bull's-eye maculopathy. Functionalclassification. Doc. Ophthalmo!. 58:257, 1984.
9. Lawwill, T., Appleton, B., and Altstatt, 1.: Chloroquine accumulations in human eyes. Am. J. Ophthalmo!.65:530, 1968.
10. Krill, A. E., Deutman, A. F., and Fishman, M.: Thecone degeneration. Doc. Ophthalmo!. 35:1, 1973.
