Geographic Atrophy of the Retinal Pigment Epithelium A Manifestation of Senile Macular
Degeneration
Charles J. Blair, MD
Eleven patients with geographic atrophy of the retinal pigment epithelium secondary to senile macular degeneration are differentiated from central areolar choroidal sclerosis. Although these lesions appear morphologically similar to central areolar choroidal sclerosis, they differ strikingly in age of onset, family history, association with senile disciform macular degeneration, and pathologic features.
picture The clinical degeneration
of senile mac¬ varies greatly and can be confused with other dis¬ ease entities. The following are a few of the manifestations that have been described: drusen in the macula with derangement of the retinal pigment epithelium; serous detachment of the retinal pigment epithelium or retina or both, giving rise to disciform le¬ sions of the macula1; hemorrhagic de¬ tachment of the retinal pigment epi¬ thelium giving rise to dark lesions in the posterior pole simulating malig¬ nant melanoma25; scar formation in the macula"; hemorrhage into the vitular
Submitted for publication June 23, 1973. From the Bascom Palmer Eye Institute, and the Department of Ophthalmology, University of Miami, School of Medicine, Miami. Dr. Blair is now at the Medical Arts Building, Richmond, VA. Reprint requests to Suite 200, Medical Arts Building, Richmond, VA 23219 (Dr. Blair).
with all of its implications1; and massive subretinal exudation.7 An entity that is not commonly rec¬ ognized as a manifestation of senile macular degeneration is geographic atrophy of the retinal pigment epi¬ thelium that morphologically is quite similar to central areolar choroidal sclerosis. It is the purpose of this report to present 11 cases with geographic at¬ rophy of the retinal pigment epithe¬ lium secondary to senile macular de¬ generation, and to differentiate this from central areolar choroidal scle¬ rosis. reous
Method The color fundus photographs were re¬ viewed in 184 consecutive patients cata¬ logued in the flies of the Bascom Palmer Eye Institute under senile macular degen¬ eration. Seventeen patients (9.2%) had a fundus pattern of geographic atrophy of the retinal pigment epithelium morpholog¬ ically similar to central areolar choroidal sclerosis. Six of these patients were ex¬ cluded from the series because of incom¬ plete information; of the remaining 11
patients, 8 were examined. Indirect ophthalmoscopy, fundus biomicroscopy with the Hruby or Goldmann lens were em¬ ployed in addition to obtaining a complete history and performing an ocular examina¬ tion. Fluorescein angiography was per¬ formed in ten of the 11 patients. The eyes
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of one patient were obtained at autopsy and were available for histologie studies.
Results Clinical Findings.—The pertinent findings in each case are listed in the Table. The areas of geographic at¬ rophy of the retinal pigment epithe¬
lium
circular to oval and were sharply demarcated (Fig 1).
were
usually Occasionally they
were more
irregu¬
lar and less defined (Fig 2). Their size ranged from one half of a disc diame¬ ter (Fig 3, left) to 3 disc diameters (Fig 4). There was peripapillary at¬ rophy of the retinal pigment epithe¬ lium to a varying degree in all patients (Fig 5, bottom right). The choroidal vessels were visible in all cases and varied in color from red to pale yellow. Drusen were present in both eyes of all cases and were most numerous in the posterior pole (Fig 6, top left and top right, 7, and 8). The lesions were single in nine cases and multiple in two. All cases demon¬ strated other evidence of senile dis¬ ciform macular degeneration ranging from disturbance of the retinal pig¬ ment epithelium and drusen in all cases (Fig 5, bottom right), to serous or cicatricial detachment of the retina and retinal pigment epithelium in three cases (Fig 5, top left, 9, left, and 10, left). The lesions were bilateral in
six
and unilateral in five. When bilateral, the lesions were usually symmetrical in size and configura¬ tion. Five men and six women were in¬ volved. All of the patients were white, but it is hard to determine the impor¬ tance of this in that a large majority of patients seen in the private clinic at the Bascom Palmer Eye Institute are white. No correlation could be made with any systemic illness. A de¬ tailed family history showed no evi¬ dence of abnormality in all cases. However, no family members were examined by the author. The age of onset was 55 to 85 years old, with an average age of onset of 74 years. The nature of onset was generally in¬ sidious (eight out of 11 cases) with gradual progression. The duration of symptoms ranged from two months to 18 years. In general, the history in¬ dicated gradual deterioration of vi¬ sion. In no case had visual function improved. Visual acuity in the 17 in¬ volved ranged from 20/50 to counting fingers at one foot. Visual acuity in 12 of these eyes was 20/300 or less. cases
Fig 1 .—Both eyes of patient 1 show symmetrical areas of atrophy of pigment epithe¬ lium with sclerotic-appearing choroidal vessels. Note pigment clumping in each le¬ sion, as well as symmetry of lesions.
Fig 2—Both eyes of patient 2 show large irregular areas of pigment epithelial atrophy with visible choroidal vessels, and scattered drusen.
Angiography.—Fluoresangiography was done in ten
Fluorescein
cein
and showed considerable at¬ rophy of the pigment epithelium in the involved areas, with the back¬ ground choroidal fluorescence coming through brightly. The choroidal ves¬ sels generally appeared to fill with fluorescein (Fig 6, bottom left). Dru¬ sen were a prominent feature seen on angiography in all eyes, more concen¬ trated in the posterior pole (Fig 6, bottom right). cases
Report
of Cases
Fig 3.—Right eye (left), shows multiple areas of pigment epithelial atrophy; left eye (right) atrophy of peripapillary pigment epithelium and scattered drusen (case 3).
The following case report is presented in detail because it demonstrates a possible mechanism for the development of the le¬ sion. (This case has been presented previ¬
ously.")
Case 5.—An 85-year-old white man was first seen in December 1963, with a sixmonth history of painless progressive loss of vision in his left eye. Visual acuity at that time was 20/40 in the right eye and 20/200 in the left eye with bilateral poste¬ rior subcapsular cataracts. His fundi were normal except for drusen in the posterior poles. His visual acuity progressively de¬ creased to 20/80 in the right eye and hand movements in the left eye. In February
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1968, he underwent
an
uneventful intra-
capsular cataract extraction on the left eye with
a
best corrected vision of 20/30. On
July 30, 1968, he underwent an uneventful intracapsular cataract extraction in the right eye and was discharged on Aug 4, 1968, after an uneventful immediate post¬ operative course. On Aug 15,1968, on a fol¬ low-up visit, he was noted to have a serous detachment of the retinal pigment epithe¬ lium in the macular area of the right eye (Fig 5, top left) that was confirmed by fluorescein angiography (Fig 5, top right). This was still present on Sept 25, 1968. On Oct 23, 1968, the serous detachment had absorbed, except for inferonasally, leaving a well-demarcated area of pigment epithe¬ lial atrophy with underlying, visible sclerotic-appearing choroidal vessels (Fig 5, bottom left). This has remained stable, and best corrected vision is 20/300 in the right eye. His left fundus had dru¬ sen in the posterior pole, some disturbance of the retinal pigment epithelium in the macula, and a prominent area of pigment atrophy around the disc (Fig 5, bottom
right).
The following case is presented in detail because the eyes were obtained for histo¬ logie examination. (The histopathologic
findings
were
previously reported.8)
Case 11.—A 76-year-old white woman had been followed up at the Bascom Palmer Eye Clinic for several years be¬ cause of senile disciform macular degener¬ ation. She had noted progressive loss of vi¬ sion in both eyes for approximately four years prior to her death. Her family his¬ tory indicated no ocular problems. Her ocu¬ lar examination showed a best corrected vision of 20/80 in each eye one year before her death. Her fundus examination at that time demonstrated a well-demarcated area of atrophy of the pigment epithelium in the maculae of both eyes, with sclerotic-ap¬ pearing choroidal vessels beneath. There were scattered drusen and peripapillary atrophy of the retinal pigment epithelium. The patient died of an acute myocardial in¬ farction and the eyes were obtained for pathologic examination. Gross examination of both eyes showed scattered drusen in the posterior pole and well-demarcated oval zones of atrophy of the retinal pigment epithelium measuring 2-disc diameters in both maculae. Microscopically (Fig 11), there was thickening of the intracapillary stroma of the choriocapillaris in the macular region, with relative absence of erythrocytes in their lumens compared with other areas. The retinal pigment epithelium was atro¬ phie within the well-demarcated area, and there was a sharp zone of transition to rel¬ atively normal pigment epithelium at the
Fig 4.—Both eyes of patient 4 show large oval areas of atrophy of retinal pigment epi¬ thelium with underlying visible sclerotic-appearing vessels and scattered drusen. Note that lesions are fairly symmetrical.
Fig 5.—Top left, Appearance of macula of right eye on Aug 15, 1968, with serous de¬ tachment of pigment epithelium (arrow). Top right, Fluorescein angiography (late phase) demonstrates fluorescein in pigment epithelial detachment. Bottom left, Appearance of macula on Oct 23,1968, after most of serous fluid had been absorbed. Note that pigment epithelium has atrophied with underlying visible sclerotic-appearing vessels. Inferonasally is a hemorrhagic detachment of retinal pigment epithelium (arrow). Bottom right, Left eye. Scattered drusen and atrophy of peripapillary pigment epithelium (case 5). (From Gass.8)
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edge.
There was fibrous metaplasia of the retinal pigment epithelium in the lesion. There were scattered areas of pigment epi¬ thelial degeneration throughout the eye. Bruch membrane showed areas of calcific degeneration and there were large drusen excrescences in many areas through the posterior pole. The larger choroidal vessels appeared normal without evidence of scle¬ rosis. There was a zone of atrophy of the pigment epithelium adjacent to the tempo¬ ral margin of the disc. There were changes in the retina attributed to postmortem ar¬ tifact.
Comment
Nettleship9 first described the en¬ tity of central senile areolar choroi¬ dal atrophy. He included the term "senile" in his description because he believed the lesion was caused by se¬ nile changes in the choroidal vessels
Fig 6.—Top, Both eyes of patient 6 show well-demarcated atrophy of pigment epithe¬ sclerotic-appearing choroidal vessels and scattered drusen. Note lesions are fairly symmetrical. Bottom left, Right eye, early fluorescein phase showing filling of smaller choroidal vessels. Bottom right, Right eye, late fluorescein phase showing trans¬ lium with
mission of choroidal fluorescence and drusen.
Fig 7.—Both eyes of patient 7 show lium with scattered drusen.
multiple areas of atrophy of retinal pigment epithe¬
of the eye. Wood,10 Fridenwald,11 and Gass8 have also implicated senile changes in the choroid as important in the pathogenesis of such lesions. In 1939, Sorsby12 described two brothers with bilateral central areolar choroidal sclerosis, both of whom had the onset of decreased vision around 20 years of age. In 1953, Sorsby and Crick11 reported four additional fam¬ ilies with central areolar choroidal sclerosis. The age of onset was the 20s in two families, and the late 40s in one family. In the fourth family, the age of onset was not determined. The fully developed lesion with well-de¬ marcated exposure of the choroidal vessels was not seen under 50 years of age. In three of these families, the af¬ fection was observed in siblings only; in the fourth, in a mother and daugh¬ ter. The authors thought that "the classical designation of central senile areolar choroidal atrophy is unwar¬ ranted insofar as it stresses senility and atrophy as essential features," and that "it is only in old age that the advanced stage of central areolar choroidal sclerosis has been recog¬ nized, but the affection itself is essen¬ tially one of early and middle life." They proposed that the term "central areolar choroidal sclerosis" be used and that such lesions were "pathognomonic" of the dominantly inherited
genetic entity.
Ashton14 described the
ologic findings from
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one
histopathSorsby's
of
of central areolar choroidal scle¬ rosis. He found a well-demarcated avascular zone extending from the submacular region to the disc. The choroid was atrophie and fibrosed with disappearance of nearly all of the choroidal vessels. The retinal pig¬ ment epithelium and outer retinal layers had disappeared without glial replacement. There was no evidence of arteriosclerotic changes within the choroidal vessels. He concluded that the findings suggested vascular at¬ rophy rather than choroidal angiosclerosis. Ferry, Llovera, and Shafer" examined a case pathologically and found that the retinal pigment epi¬ thelium was absent, the choriocapil¬ laris was obliterated, and the remain¬ ing choroid was atrophie. The cases presented in this report differ strikingly in many respects from those described by Sorsby and cases
Fig 8.—Left, Note numerous drusen and peripapillary atrophy of pigment epithelium of right eye. Right, Well-demarcated oval area of pigment epithelial atrophy with underlying visible sclerotic-appearing choroidal vessels in left eye (case 8). Fig 9.—Left, Serous detachment of retinal pigment drusen in right eye. Right, Irregular area of atrophy of drusen in left eye (case 9).
epithelium (arrow) with pigment epithelium with
scattered scattered
Crick,13 although morphologically they are very similar. The age of on¬
Fig 10.—Left, Old cicatricial detachment of retinal pigment epithelium (black arrow) with scattered drusen in right eye. Note subpigment epithelial neovascularization arising from choroid (white arrow). Right, Irregular well-demarcated area of atrophy of pigment epithelium and visible choroidal vessels in left eye (case 10).
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set of symptoms was much later in life than Sorsby's cases. There was family history of disease in Sorsby's cases and no history in these cases. All of Sorsby's cases showed bilateral involvement, whereas only six of 11 patients had bilateral involvement in the present series. In Sorsby's cases, drusen were not described, whereas in the present series, this was a con¬ spicuous feature. The pathologic fea¬ tures also differed as previously de¬ scribed. It is evident from the aforemen¬ tioned that we are dealing with two different disease entities with similar ophthalmoscopic features. The lesions presented by Sorsby represent an in¬ herited disease becoming symptomat¬ ic relatively early in life, while the le¬ sions in this series are a consequence of senile changes becoming sympto¬ matic relatively late in life. It is suggested that the term geographic atrophy of the retinal pigment epi¬ thelium secondary to senile macular degeneration be used to describe the latter. It has been our experience that the senile variety occurs much more frequently than the inherited variety. Gass1 described the pathogenesis of senile disciform macular degenera¬ tion resulting from encroachment on the choriocapillaris bed by the thick-
Summary of Clinical
ening of the intercapillary stroma with the irregular thickening and de¬ generation of Bruch membrane. This results in the loss of normal adhesion between the pigment epithelium and Bruch membrane, with ingrowth of new vessels from the choriocapillaris into the subpigment epithelial space. This sets the stage for serous or hemorrhagic detachment of the pigment epithelium. Once the pigment epithe¬ lium detaches, the overlying pigment epithelial cells and neurosensory cells of the retina undergo degeneration. If the serous or hemorrhagic fluid is reabsorbed, this would leave a welldemarcated area of atrophy of the pigment epithelium through which the underlying choroidal vessels could be seen. The well-deiinarcated borders of a pigment epithelial detachment would explain the well-demarcated borders of pigment epithelial at¬ rophy. A diagrammatic representa¬ tion of this mechanism is outlined in Fig 12. Case 5, as previously de¬ scribed, demonstrates this course of events.
Another possible mechanism for fo¬ cal atrophy of the pigment epithelium and neurosensory retina would be fo¬ cal ischemie changes in the underFig 11.—Microscopical section taken at margin of lesion in right eye. Note abrupt atrophy and metaplasia of pigment epithe¬ lium at this point (arrow). Bruch mem¬ brane shows areas of calcific degenera¬
tion and thickening. There is a relative paucity of blood cells in choriocapillaris. Larger choroidal vessels appear normal (case 11, hematoxylin-eosin, original mag¬ nification 200). (From Gass.8)
Data*
Vision
Case
No.t/
Age/Sex/
Figure No.
1/64/M/1 2/68/F/2
Duration, Progression, and Eye Involved 8yr,
(Best Corrected) OD CF 2 ft
OS CF 1 foot
gradually pro¬ gressive, OU
CF8ft
3 mo,
gradually pro¬
fairly sharp 20/80-2
20/30
gressive, OD
4/71/M/4
20/300
12 yr,
gradually
20/300
pro¬
3 mo,
6/55/F/6
7yr,
stable,
20/300
20/30
5/200
20/50
OD
gradually
pro¬
18 yr,
8/69/F/8
gressive, OU 3yr,
gradually pro¬ gradually pro¬
2 mo,
10/60/F/10
7yr,
Pink
Pink to
2.0X1.5,
Yellow
oval, sharp 1.5X2.0, circular,
yellow
Pink to
yellow Pink
20/30
20/400
2X1, oval,
Pink to
0.5X1.0,
sharp sharp
yellow
CF14ft
CF6ft
1X1, irregular oval
Pink
5/400
20/70-2
1.5X2.0,
Red to
sharp
irregular oval
pro¬
sharp
gressive, OS 4 yr,
gradually
yellow
5-6 areas OU
OS
11/76/F/11
Pink to
20/400
stable, gradually
yellow
20/400
gressive, OS
9/81/M/9
Vessels Pink to
0.5X1.0, oval, sharp 2.5X2.0, OU oval,
sharp
gressive, OU
7/55/F/7
5-6 areas
sharp
gressive, OU
5/85/M/5
3X3,
OU circular,
gradually pro¬
gressive, OU
3/68/M/3
Demarcation
1.5X1.5, OU circular,
sharp
CFIOft
5yr,
Size (in Disc Diameters), Shape Color of of Lesion, and Choroidal
20/80
progressive, OU
20/80
2X2, OU irregular oval, sharp
yellow Pink to
yellow
* All patients included in this table were white. There were no family histories of abnor¬ malities. t Except for patient 11 with hypertension and patients 1 and 4 with coronary artery disease, the other patients had no medical histories of disease. Drusen and peripapillary atrophy were present in both eyes throughout the series. Except for patients 1, 5, and 9 who had sudden onset of visual disturbance, the other onsets were insidious.
Fig 12.—Proposed pathogenesis of geographic atrophy of retinal pigment epithelium. A, Serous detachment of retinal pigment epithelium secondary to senile macular degen¬ eration; B, atrophy of retinal pigment epithelium and neuroreceptors; C and D, absorp¬ tion of serous fluid leaving circumscribed zone of atrophy of retinal pigment epithelium and neuroreceptors, "a window into the choroid." R indicates retina; R & C, rods and cones; RPE, retinal pigment epithelium; SF, serous fluid; BM, Bruch membrane; CC, choriocapillaris; C, larger choroidal vessels; S, sclera.
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without serous detachment of the retinal pigment epithelium. It is difficult, however, to understand how such a mechanism would give rise to such a well-demar¬ cated area of atrophy of the retinal
in its course and would change in color from yellow to reddish orange as it passed beneath the margin of the lesion into an area where the pigment
The sclerotic appearance of the larger choroidal vessels in the lesions is undoubtedly due primarily to the absence of the retinal pigment epi¬ thelium, which normally alters their color. Often a single sclerotic appear¬ ing choroidal vessel could be followed
vessels. Gass16 has presented evidence that senile macular degeneration can be inherited on an autosomal dominant basis. In the present study, there were no family histories of disease, but it should be emphasized that the
lying choriocapillaris
pigment epithelium.
epithelium was relatively normal. Pathologically, there was no evidence of sclerosis of the larger choroidal
author did not examine other members.
family
This investigation was supported in part by Special Fellowship Award 1F11 NB1943 from the National Institutes of Neurological Diseases and Blindness. J. Donald M. Gass, MD, gave permission to use cases 5 and 11. Joseph Goren and Johnny Justice assisted in preparing the fundus photographs.
Key Words.—Central areolar choroidal
sclerosis; geographic atrophy of the retinal pigment epithelium; drusen; macula; senile macular degeneration.
References 1. Gass JDM: Pathogenesis of disciform detachment of the neuroepithelium: III. Senile disciform macular degeneration. Am J Ophthalmol 63:617-644, 1967. 2. Zscheile FP: Disciform lesion of the macula simulating a melanoma. Arch Ophthalmol 71:505-507, 1964. 3. Zimmerman LE: Macular diseases: Differential diagnosis: Macular lesion mistaken for malignant melanoma of choroid. Trans Am Acad Ophthalmol Otolaryngol 69:623-625, 1965. 4. Ferry AP: Lesions mistaken for malignant melanoma of the posterior uvea: A clinicopathologic analysis of 100 cases with ophthalmoscopically visible lesions. Arch Ophthalmol 72:463-469, 1964. 5. Frayer WC: Elevated lesion of the macular
area: A histopathologic study emphasizing lesions similar to disciform degeneration. Arch Ophthalmol 53:82-92, 1955. 6. Junius P, Kuhnt H: Die scheibenformige Entartung der Netzhautmitte (Degeneratio maculae luteae disciformis). Berlin, Karger, 1926. 7. Blair CJ, Aaberg TM: Massive subretinal exudation associated with senile macular degeneration. Am J Ophthalmol 71:639-648, 1971. 8. Gass JDM: Stereoscopic Atlas of Macular Diseases, St. Louis, The CV Mosby Co, 1970. 9. Nettleship E: Central senile areolar choroidal atrophy. Trans Ophthalmol Soc UK 4:165, 1884. 10. Wood CGR: Choroidal sclerosis. The Ophthalmoscope 13:374-376, 1915. 11. Fridenwald JS: The Pathology of the Eye.
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 05/28/2015
New York, The MacMillan Co, Publishers, 1929. 12. Sorsby A: Choroidal angio-sclerosis with special reference to its hereditary character. Br J Ophthalmol 23:433-444, 1939. 13. Sorsby A, Crick RP: Central areolar choroidal sclerosis. Br J Ophthalmol 37:129-139, 1953. 14. Ashton N: Central areolar choroidal sclerosis. A histopathological study. Br J Ophthalmol 37:140-147, 1953. 15. Ferry AP, Llovera I, Shafer DM: Central areolar choroidal dystrophy. Arch Ophthalmol 88:39-43, 1972. 16. Gass JDM: Drusen and disciform macular detachment and degeneration. Trans Am Ophthalmol Soc 70:409-436, 1972.
Degeneration
Charles J. Blair, MD
Eleven patients with geographic atrophy of the retinal pigment epithelium secondary to senile macular degeneration are differentiated from central areolar choroidal sclerosis. Although these lesions appear morphologically similar to central areolar choroidal sclerosis, they differ strikingly in age of onset, family history, association with senile disciform macular degeneration, and pathologic features.
picture The clinical degeneration
of senile mac¬ varies greatly and can be confused with other dis¬ ease entities. The following are a few of the manifestations that have been described: drusen in the macula with derangement of the retinal pigment epithelium; serous detachment of the retinal pigment epithelium or retina or both, giving rise to disciform le¬ sions of the macula1; hemorrhagic de¬ tachment of the retinal pigment epi¬ thelium giving rise to dark lesions in the posterior pole simulating malig¬ nant melanoma25; scar formation in the macula"; hemorrhage into the vitular
Submitted for publication June 23, 1973. From the Bascom Palmer Eye Institute, and the Department of Ophthalmology, University of Miami, School of Medicine, Miami. Dr. Blair is now at the Medical Arts Building, Richmond, VA. Reprint requests to Suite 200, Medical Arts Building, Richmond, VA 23219 (Dr. Blair).
with all of its implications1; and massive subretinal exudation.7 An entity that is not commonly rec¬ ognized as a manifestation of senile macular degeneration is geographic atrophy of the retinal pigment epi¬ thelium that morphologically is quite similar to central areolar choroidal sclerosis. It is the purpose of this report to present 11 cases with geographic at¬ rophy of the retinal pigment epithe¬ lium secondary to senile macular de¬ generation, and to differentiate this from central areolar choroidal scle¬ rosis. reous
Method The color fundus photographs were re¬ viewed in 184 consecutive patients cata¬ logued in the flies of the Bascom Palmer Eye Institute under senile macular degen¬ eration. Seventeen patients (9.2%) had a fundus pattern of geographic atrophy of the retinal pigment epithelium morpholog¬ ically similar to central areolar choroidal sclerosis. Six of these patients were ex¬ cluded from the series because of incom¬ plete information; of the remaining 11
patients, 8 were examined. Indirect ophthalmoscopy, fundus biomicroscopy with the Hruby or Goldmann lens were em¬ ployed in addition to obtaining a complete history and performing an ocular examina¬ tion. Fluorescein angiography was per¬ formed in ten of the 11 patients. The eyes
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 05/28/2015
of one patient were obtained at autopsy and were available for histologie studies.
Results Clinical Findings.—The pertinent findings in each case are listed in the Table. The areas of geographic at¬ rophy of the retinal pigment epithe¬
lium
circular to oval and were sharply demarcated (Fig 1).
were
usually Occasionally they
were more
irregu¬
lar and less defined (Fig 2). Their size ranged from one half of a disc diame¬ ter (Fig 3, left) to 3 disc diameters (Fig 4). There was peripapillary at¬ rophy of the retinal pigment epithe¬ lium to a varying degree in all patients (Fig 5, bottom right). The choroidal vessels were visible in all cases and varied in color from red to pale yellow. Drusen were present in both eyes of all cases and were most numerous in the posterior pole (Fig 6, top left and top right, 7, and 8). The lesions were single in nine cases and multiple in two. All cases demon¬ strated other evidence of senile dis¬ ciform macular degeneration ranging from disturbance of the retinal pig¬ ment epithelium and drusen in all cases (Fig 5, bottom right), to serous or cicatricial detachment of the retina and retinal pigment epithelium in three cases (Fig 5, top left, 9, left, and 10, left). The lesions were bilateral in
six
and unilateral in five. When bilateral, the lesions were usually symmetrical in size and configura¬ tion. Five men and six women were in¬ volved. All of the patients were white, but it is hard to determine the impor¬ tance of this in that a large majority of patients seen in the private clinic at the Bascom Palmer Eye Institute are white. No correlation could be made with any systemic illness. A de¬ tailed family history showed no evi¬ dence of abnormality in all cases. However, no family members were examined by the author. The age of onset was 55 to 85 years old, with an average age of onset of 74 years. The nature of onset was generally in¬ sidious (eight out of 11 cases) with gradual progression. The duration of symptoms ranged from two months to 18 years. In general, the history in¬ dicated gradual deterioration of vi¬ sion. In no case had visual function improved. Visual acuity in the 17 in¬ volved ranged from 20/50 to counting fingers at one foot. Visual acuity in 12 of these eyes was 20/300 or less. cases
Fig 1 .—Both eyes of patient 1 show symmetrical areas of atrophy of pigment epithe¬ lium with sclerotic-appearing choroidal vessels. Note pigment clumping in each le¬ sion, as well as symmetry of lesions.
Fig 2—Both eyes of patient 2 show large irregular areas of pigment epithelial atrophy with visible choroidal vessels, and scattered drusen.
Angiography.—Fluoresangiography was done in ten
Fluorescein
cein
and showed considerable at¬ rophy of the pigment epithelium in the involved areas, with the back¬ ground choroidal fluorescence coming through brightly. The choroidal ves¬ sels generally appeared to fill with fluorescein (Fig 6, bottom left). Dru¬ sen were a prominent feature seen on angiography in all eyes, more concen¬ trated in the posterior pole (Fig 6, bottom right). cases
Report
of Cases
Fig 3.—Right eye (left), shows multiple areas of pigment epithelial atrophy; left eye (right) atrophy of peripapillary pigment epithelium and scattered drusen (case 3).
The following case report is presented in detail because it demonstrates a possible mechanism for the development of the le¬ sion. (This case has been presented previ¬
ously.")
Case 5.—An 85-year-old white man was first seen in December 1963, with a sixmonth history of painless progressive loss of vision in his left eye. Visual acuity at that time was 20/40 in the right eye and 20/200 in the left eye with bilateral poste¬ rior subcapsular cataracts. His fundi were normal except for drusen in the posterior poles. His visual acuity progressively de¬ creased to 20/80 in the right eye and hand movements in the left eye. In February
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 05/28/2015
1968, he underwent
an
uneventful intra-
capsular cataract extraction on the left eye with
a
best corrected vision of 20/30. On
July 30, 1968, he underwent an uneventful intracapsular cataract extraction in the right eye and was discharged on Aug 4, 1968, after an uneventful immediate post¬ operative course. On Aug 15,1968, on a fol¬ low-up visit, he was noted to have a serous detachment of the retinal pigment epithe¬ lium in the macular area of the right eye (Fig 5, top left) that was confirmed by fluorescein angiography (Fig 5, top right). This was still present on Sept 25, 1968. On Oct 23, 1968, the serous detachment had absorbed, except for inferonasally, leaving a well-demarcated area of pigment epithe¬ lial atrophy with underlying, visible sclerotic-appearing choroidal vessels (Fig 5, bottom left). This has remained stable, and best corrected vision is 20/300 in the right eye. His left fundus had dru¬ sen in the posterior pole, some disturbance of the retinal pigment epithelium in the macula, and a prominent area of pigment atrophy around the disc (Fig 5, bottom
right).
The following case is presented in detail because the eyes were obtained for histo¬ logie examination. (The histopathologic
findings
were
previously reported.8)
Case 11.—A 76-year-old white woman had been followed up at the Bascom Palmer Eye Clinic for several years be¬ cause of senile disciform macular degener¬ ation. She had noted progressive loss of vi¬ sion in both eyes for approximately four years prior to her death. Her family his¬ tory indicated no ocular problems. Her ocu¬ lar examination showed a best corrected vision of 20/80 in each eye one year before her death. Her fundus examination at that time demonstrated a well-demarcated area of atrophy of the pigment epithelium in the maculae of both eyes, with sclerotic-ap¬ pearing choroidal vessels beneath. There were scattered drusen and peripapillary atrophy of the retinal pigment epithelium. The patient died of an acute myocardial in¬ farction and the eyes were obtained for pathologic examination. Gross examination of both eyes showed scattered drusen in the posterior pole and well-demarcated oval zones of atrophy of the retinal pigment epithelium measuring 2-disc diameters in both maculae. Microscopically (Fig 11), there was thickening of the intracapillary stroma of the choriocapillaris in the macular region, with relative absence of erythrocytes in their lumens compared with other areas. The retinal pigment epithelium was atro¬ phie within the well-demarcated area, and there was a sharp zone of transition to rel¬ atively normal pigment epithelium at the
Fig 4.—Both eyes of patient 4 show large oval areas of atrophy of retinal pigment epi¬ thelium with underlying visible sclerotic-appearing vessels and scattered drusen. Note that lesions are fairly symmetrical.
Fig 5.—Top left, Appearance of macula of right eye on Aug 15, 1968, with serous de¬ tachment of pigment epithelium (arrow). Top right, Fluorescein angiography (late phase) demonstrates fluorescein in pigment epithelial detachment. Bottom left, Appearance of macula on Oct 23,1968, after most of serous fluid had been absorbed. Note that pigment epithelium has atrophied with underlying visible sclerotic-appearing vessels. Inferonasally is a hemorrhagic detachment of retinal pigment epithelium (arrow). Bottom right, Left eye. Scattered drusen and atrophy of peripapillary pigment epithelium (case 5). (From Gass.8)
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edge.
There was fibrous metaplasia of the retinal pigment epithelium in the lesion. There were scattered areas of pigment epi¬ thelial degeneration throughout the eye. Bruch membrane showed areas of calcific degeneration and there were large drusen excrescences in many areas through the posterior pole. The larger choroidal vessels appeared normal without evidence of scle¬ rosis. There was a zone of atrophy of the pigment epithelium adjacent to the tempo¬ ral margin of the disc. There were changes in the retina attributed to postmortem ar¬ tifact.
Comment
Nettleship9 first described the en¬ tity of central senile areolar choroi¬ dal atrophy. He included the term "senile" in his description because he believed the lesion was caused by se¬ nile changes in the choroidal vessels
Fig 6.—Top, Both eyes of patient 6 show well-demarcated atrophy of pigment epithe¬ sclerotic-appearing choroidal vessels and scattered drusen. Note lesions are fairly symmetrical. Bottom left, Right eye, early fluorescein phase showing filling of smaller choroidal vessels. Bottom right, Right eye, late fluorescein phase showing trans¬ lium with
mission of choroidal fluorescence and drusen.
Fig 7.—Both eyes of patient 7 show lium with scattered drusen.
multiple areas of atrophy of retinal pigment epithe¬
of the eye. Wood,10 Fridenwald,11 and Gass8 have also implicated senile changes in the choroid as important in the pathogenesis of such lesions. In 1939, Sorsby12 described two brothers with bilateral central areolar choroidal sclerosis, both of whom had the onset of decreased vision around 20 years of age. In 1953, Sorsby and Crick11 reported four additional fam¬ ilies with central areolar choroidal sclerosis. The age of onset was the 20s in two families, and the late 40s in one family. In the fourth family, the age of onset was not determined. The fully developed lesion with well-de¬ marcated exposure of the choroidal vessels was not seen under 50 years of age. In three of these families, the af¬ fection was observed in siblings only; in the fourth, in a mother and daugh¬ ter. The authors thought that "the classical designation of central senile areolar choroidal atrophy is unwar¬ ranted insofar as it stresses senility and atrophy as essential features," and that "it is only in old age that the advanced stage of central areolar choroidal sclerosis has been recog¬ nized, but the affection itself is essen¬ tially one of early and middle life." They proposed that the term "central areolar choroidal sclerosis" be used and that such lesions were "pathognomonic" of the dominantly inherited
genetic entity.
Ashton14 described the
ologic findings from
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one
histopathSorsby's
of
of central areolar choroidal scle¬ rosis. He found a well-demarcated avascular zone extending from the submacular region to the disc. The choroid was atrophie and fibrosed with disappearance of nearly all of the choroidal vessels. The retinal pig¬ ment epithelium and outer retinal layers had disappeared without glial replacement. There was no evidence of arteriosclerotic changes within the choroidal vessels. He concluded that the findings suggested vascular at¬ rophy rather than choroidal angiosclerosis. Ferry, Llovera, and Shafer" examined a case pathologically and found that the retinal pigment epi¬ thelium was absent, the choriocapil¬ laris was obliterated, and the remain¬ ing choroid was atrophie. The cases presented in this report differ strikingly in many respects from those described by Sorsby and cases
Fig 8.—Left, Note numerous drusen and peripapillary atrophy of pigment epithelium of right eye. Right, Well-demarcated oval area of pigment epithelial atrophy with underlying visible sclerotic-appearing choroidal vessels in left eye (case 8). Fig 9.—Left, Serous detachment of retinal pigment drusen in right eye. Right, Irregular area of atrophy of drusen in left eye (case 9).
epithelium (arrow) with pigment epithelium with
scattered scattered
Crick,13 although morphologically they are very similar. The age of on¬
Fig 10.—Left, Old cicatricial detachment of retinal pigment epithelium (black arrow) with scattered drusen in right eye. Note subpigment epithelial neovascularization arising from choroid (white arrow). Right, Irregular well-demarcated area of atrophy of pigment epithelium and visible choroidal vessels in left eye (case 10).
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set of symptoms was much later in life than Sorsby's cases. There was family history of disease in Sorsby's cases and no history in these cases. All of Sorsby's cases showed bilateral involvement, whereas only six of 11 patients had bilateral involvement in the present series. In Sorsby's cases, drusen were not described, whereas in the present series, this was a con¬ spicuous feature. The pathologic fea¬ tures also differed as previously de¬ scribed. It is evident from the aforemen¬ tioned that we are dealing with two different disease entities with similar ophthalmoscopic features. The lesions presented by Sorsby represent an in¬ herited disease becoming symptomat¬ ic relatively early in life, while the le¬ sions in this series are a consequence of senile changes becoming sympto¬ matic relatively late in life. It is suggested that the term geographic atrophy of the retinal pigment epi¬ thelium secondary to senile macular degeneration be used to describe the latter. It has been our experience that the senile variety occurs much more frequently than the inherited variety. Gass1 described the pathogenesis of senile disciform macular degenera¬ tion resulting from encroachment on the choriocapillaris bed by the thick-
Summary of Clinical
ening of the intercapillary stroma with the irregular thickening and de¬ generation of Bruch membrane. This results in the loss of normal adhesion between the pigment epithelium and Bruch membrane, with ingrowth of new vessels from the choriocapillaris into the subpigment epithelial space. This sets the stage for serous or hemorrhagic detachment of the pigment epithelium. Once the pigment epithe¬ lium detaches, the overlying pigment epithelial cells and neurosensory cells of the retina undergo degeneration. If the serous or hemorrhagic fluid is reabsorbed, this would leave a welldemarcated area of atrophy of the pigment epithelium through which the underlying choroidal vessels could be seen. The well-deiinarcated borders of a pigment epithelial detachment would explain the well-demarcated borders of pigment epithelial at¬ rophy. A diagrammatic representa¬ tion of this mechanism is outlined in Fig 12. Case 5, as previously de¬ scribed, demonstrates this course of events.
Another possible mechanism for fo¬ cal atrophy of the pigment epithelium and neurosensory retina would be fo¬ cal ischemie changes in the underFig 11.—Microscopical section taken at margin of lesion in right eye. Note abrupt atrophy and metaplasia of pigment epithe¬ lium at this point (arrow). Bruch mem¬ brane shows areas of calcific degenera¬
tion and thickening. There is a relative paucity of blood cells in choriocapillaris. Larger choroidal vessels appear normal (case 11, hematoxylin-eosin, original mag¬ nification 200). (From Gass.8)
Data*
Vision
Case
No.t/
Age/Sex/
Figure No.
1/64/M/1 2/68/F/2
Duration, Progression, and Eye Involved 8yr,
(Best Corrected) OD CF 2 ft
OS CF 1 foot
gradually pro¬ gressive, OU
CF8ft
3 mo,
gradually pro¬
fairly sharp 20/80-2
20/30
gressive, OD
4/71/M/4
20/300
12 yr,
gradually
20/300
pro¬
3 mo,
6/55/F/6
7yr,
stable,
20/300
20/30
5/200
20/50
OD
gradually
pro¬
18 yr,
8/69/F/8
gressive, OU 3yr,
gradually pro¬ gradually pro¬
2 mo,
10/60/F/10
7yr,
Pink
Pink to
2.0X1.5,
Yellow
oval, sharp 1.5X2.0, circular,
yellow
Pink to
yellow Pink
20/30
20/400
2X1, oval,
Pink to
0.5X1.0,
sharp sharp
yellow
CF14ft
CF6ft
1X1, irregular oval
Pink
5/400
20/70-2
1.5X2.0,
Red to
sharp
irregular oval
pro¬
sharp
gressive, OS 4 yr,
gradually
yellow
5-6 areas OU
OS
11/76/F/11
Pink to
20/400
stable, gradually
yellow
20/400
gressive, OS
9/81/M/9
Vessels Pink to
0.5X1.0, oval, sharp 2.5X2.0, OU oval,
sharp
gressive, OU
7/55/F/7
5-6 areas
sharp
gressive, OU
5/85/M/5
3X3,
OU circular,
gradually pro¬
gressive, OU
3/68/M/3
Demarcation
1.5X1.5, OU circular,
sharp
CFIOft
5yr,
Size (in Disc Diameters), Shape Color of of Lesion, and Choroidal
20/80
progressive, OU
20/80
2X2, OU irregular oval, sharp
yellow Pink to
yellow
* All patients included in this table were white. There were no family histories of abnor¬ malities. t Except for patient 11 with hypertension and patients 1 and 4 with coronary artery disease, the other patients had no medical histories of disease. Drusen and peripapillary atrophy were present in both eyes throughout the series. Except for patients 1, 5, and 9 who had sudden onset of visual disturbance, the other onsets were insidious.
Fig 12.—Proposed pathogenesis of geographic atrophy of retinal pigment epithelium. A, Serous detachment of retinal pigment epithelium secondary to senile macular degen¬ eration; B, atrophy of retinal pigment epithelium and neuroreceptors; C and D, absorp¬ tion of serous fluid leaving circumscribed zone of atrophy of retinal pigment epithelium and neuroreceptors, "a window into the choroid." R indicates retina; R & C, rods and cones; RPE, retinal pigment epithelium; SF, serous fluid; BM, Bruch membrane; CC, choriocapillaris; C, larger choroidal vessels; S, sclera.
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without serous detachment of the retinal pigment epithelium. It is difficult, however, to understand how such a mechanism would give rise to such a well-demar¬ cated area of atrophy of the retinal
in its course and would change in color from yellow to reddish orange as it passed beneath the margin of the lesion into an area where the pigment
The sclerotic appearance of the larger choroidal vessels in the lesions is undoubtedly due primarily to the absence of the retinal pigment epi¬ thelium, which normally alters their color. Often a single sclerotic appear¬ ing choroidal vessel could be followed
vessels. Gass16 has presented evidence that senile macular degeneration can be inherited on an autosomal dominant basis. In the present study, there were no family histories of disease, but it should be emphasized that the
lying choriocapillaris
pigment epithelium.
epithelium was relatively normal. Pathologically, there was no evidence of sclerosis of the larger choroidal
author did not examine other members.
family
This investigation was supported in part by Special Fellowship Award 1F11 NB1943 from the National Institutes of Neurological Diseases and Blindness. J. Donald M. Gass, MD, gave permission to use cases 5 and 11. Joseph Goren and Johnny Justice assisted in preparing the fundus photographs.
Key Words.—Central areolar choroidal
sclerosis; geographic atrophy of the retinal pigment epithelium; drusen; macula; senile macular degeneration.
References 1. Gass JDM: Pathogenesis of disciform detachment of the neuroepithelium: III. Senile disciform macular degeneration. Am J Ophthalmol 63:617-644, 1967. 2. Zscheile FP: Disciform lesion of the macula simulating a melanoma. Arch Ophthalmol 71:505-507, 1964. 3. Zimmerman LE: Macular diseases: Differential diagnosis: Macular lesion mistaken for malignant melanoma of choroid. Trans Am Acad Ophthalmol Otolaryngol 69:623-625, 1965. 4. Ferry AP: Lesions mistaken for malignant melanoma of the posterior uvea: A clinicopathologic analysis of 100 cases with ophthalmoscopically visible lesions. Arch Ophthalmol 72:463-469, 1964. 5. Frayer WC: Elevated lesion of the macular
area: A histopathologic study emphasizing lesions similar to disciform degeneration. Arch Ophthalmol 53:82-92, 1955. 6. Junius P, Kuhnt H: Die scheibenformige Entartung der Netzhautmitte (Degeneratio maculae luteae disciformis). Berlin, Karger, 1926. 7. Blair CJ, Aaberg TM: Massive subretinal exudation associated with senile macular degeneration. Am J Ophthalmol 71:639-648, 1971. 8. Gass JDM: Stereoscopic Atlas of Macular Diseases, St. Louis, The CV Mosby Co, 1970. 9. Nettleship E: Central senile areolar choroidal atrophy. Trans Ophthalmol Soc UK 4:165, 1884. 10. Wood CGR: Choroidal sclerosis. The Ophthalmoscope 13:374-376, 1915. 11. Fridenwald JS: The Pathology of the Eye.
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New York, The MacMillan Co, Publishers, 1929. 12. Sorsby A: Choroidal angio-sclerosis with special reference to its hereditary character. Br J Ophthalmol 23:433-444, 1939. 13. Sorsby A, Crick RP: Central areolar choroidal sclerosis. Br J Ophthalmol 37:129-139, 1953. 14. Ashton N: Central areolar choroidal sclerosis. A histopathological study. Br J Ophthalmol 37:140-147, 1953. 15. Ferry AP, Llovera I, Shafer DM: Central areolar choroidal dystrophy. Arch Ophthalmol 88:39-43, 1972. 16. Gass JDM: Drusen and disciform macular detachment and degeneration. Trans Am Ophthalmol Soc 70:409-436, 1972.
