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Drusen of the Optic Disk in Retinitis Pigmentosa
Drusen of the Optic Disk in Retinitis Pigmentosa Roger L. Novack, M . D . , and Robert Y. Foos, M . D .
To clarify the nature of mulberry-like excresences of the optic disk, we histopathologically studied the eye of a 66-year-old wom an with retinitis pigmentosa. Examination showed that the optic nerve excresences were ordinary drusen and not hamartomas. There was a marked predisposition to mineralization of other intraocular structures. THERE IS A continuing controversy concern ing the nature of the mulberry-like lesions of the optic disk in patients with retinitis pigmen tosa. Some investigators consider the lesions to be astrocytic hamartomas, while others have identified them as ordinary drusen of the optic disk. The present report, which is based on a pathologic study of an eye from a 66-year-old woman with retinitis pigmentosa, supports the conclusions of the two prior histopathologic investigations. The mulberry-like masses of the optic disk are drusen, not hamartomas. Our case also showed a marked predisposition to mineralization of other intraocular structures.
the family. The patient was legally blind by age 11 years and lost all light perception 15 years before her death. Two of her sisters became blind in their late 20s. The patient's only child, a daughter now in her late 30s, has normal vision. Two years before the patient's death, ophthalmoscopic examination of both eyes showed bone spicule pigmentation in the entire extramacular retina. There were attenuated retinal vessels and multiple small lesions over both optic nerves. Asteroid hyalosis was described in the vitreous. An electroretinogram per formed before loss of light perception was noted as "markedly abnormal" on medical re ports. The patient's eyes were enucleated within three hours of death. The right eye was used in an attempt to develop a cell culture line by the cell biology group at our institution. The left eye was fixed for gross pathology and study by light and electron microscopy. Reported here are the findings of the optic disk by light mi croscopy.
Case Report The patient, a 66-year-old woman, died of congestive heart failure. She had 11 siblings: four brothers and seven sisters. Three of her sisters developed retinitis pigmentosa al though there was no history of retinitis pig mentosa or other ocular disease in either side of
Accepted for publication Sept. 29, 1986. From the Jules Stein Eye Institute and the School of Medicine, University of California, Los Angeles. This study was supported in part by Public Health Service Center Grant EY 00331; National Eye Institute research grant EY 00725; Research Manpower Award (Dr. Foos), Research to Prevent Blindness, Inc.; Research Grant-inAid (Dr. Novack), National Society to Prevent Blind ness, New York; and research support (Dr. Novack), The Adler Foundation, Inc. Reprint requests to Robert Foos, M.D., Jules Stein Eye Institute, 800 Westwood Plaza, Los Angeles, CA 90024.
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Fig. 1 (Novack and Foos). Gross section of the optic nerve head. A ring of yellow hyaline globules is seen at the outer margin of the optic disk and in parapapillary retina (x25).
©AMERICAN JOURNAL OF OPHTHALMOLOGY 103:44-47, JANUARY, 1987
Vol. 103, No. 1
Optic Disk Drusen in Retinitis Pigmentosa
45
Fig. 2 (Novack and Foos). Nasal and temporal calottes of the left eye. Dense asteroid hyalosis of the vitreous is seen (x3.4). The optic nerve measured 2 mm in length and was crushed. The left eye was opened vertically, temporal to the optic disk. The block containing the optic disk was washed, decalci fied for 24 hours in a solution of formic acid and sodium citrate, and processed for embedding in paraffin. The block was cut in 6-u.m sections and stained with hematoxylin and eosin. Rou tine stains were supplemented with periodic acid-Schiff reaction. On internal examination, dense spicular pig mentation was noted throughout the retina with relative sparing of the macula. The retinal vasculature was attenuated. A ring of yellow hyaline globules was seen at the margin of the optic disk and in the parapapillary retina (Fig. 1). There was dense asteroid hyalosis of the vitreous (Fig. 2). Light microscopy showed laminated acellular masses of different sizes and shapes located within the substance of the optic disk anterior to the scleral lamina cribrosa (Fig. 3), deep in the parapapillary retina (Fig. 4), and extruded
Fig. 4 (Novack and Foos). Light micrograph section shows a large laminated acellular parapapillary mass and two smaller masses of similar composition locat ed deep in the parapapillary retina. Calcification of the inner limiting lamina is also evident (arrow) (see Fig. 6) (hematoxylin and eosin, x 125).
Fig. 3 (Novack and Foos). Light micrograph section of the optic nerve and disk demonstrates laminated acellular masses of different sizes and shapes located within the substance of the optic disk, anterior to the scleral lamina cribrosa, and extruded from the optic disk and parapapillary retina (periodic acid-Schiff preparation, x 50). from the optic disk and parapapillary retina (Fig. 3). Corpora amylacea were present in the optic disk and the optic nerve (Fig. 5). In some areas, calcification of the inner limiting lamina was evident (Fig. 6). A string of mineralized deposits was seen lying under the basal lamina and surface of the optic disk (Fig. 7).
Discussion The nature of the lesions of the optic disk seen in retinitis pigmentosa have been widely discussed. Robertson 1 suggested that the mulberry-like masses seen on the optic nerve in retinitis pigmentosa were hamartomas. This
corpora amylacea present in the optic disk and optic nerve (arrows) (periodic acid-Schiff preparation, x 680).
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AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 6 (Novack and Foos). Light micrograph of calcified inner limiting lamina. Astrogliosis is also evident in the underlying optic disk (hematoxylin and eosin, x680). identification was made clinically and without histopathologic confirmation. His conclusions were supported by DeBustros and associates 2 and Pillai, Limaye, and Saimovici, 3 whose findings were also based on clinical studies. These studies suggested that the lesions are glial proliferations of hamartomas and not drusen. Hogan and Zimmerman 4 emphasized that both hamartomas and drusen are present in the optic disk. They described drusen of the optic disk as laminated acellular basophilic con cretions that are situated anterior to the lamina cribrosa and only infrequently reach the sur face of the nerve head. In contrast, optic disk hamartomas were described as calcifications and proliferations of astrocytic cells in the parapapillary retina.1-4 Our case is the third report of optic nerve head drusen associated with retinitis pigmentosa that has been studied histopathologically . 5 6 Miiller5 used drawings to illustrate lesions in the optic nerve head but not in the parapapillary retina. This supported the con clusion of Puck, Tso, and Fishman 6 that the drusen were ordinary and not astrocytic ham artomas as suggested previously. 1 ' 3 As in the report of Puck, Tso, and Fishman, the drusen in our specimen are largely in the more superficial aspect of the optic disk, but also involve the parapapillary retina at all lev els. Spencer, 7 Seitz and Kersting, 8 and Seitz9 propose that drusen of the optic disk are the end result of axonal degeneration. Based on
January, 1987
Fig. 7 (Novack and Foos). Light micrograph of the optic nerve head and parapapillary region shows a string of mineralized deposits underlying the basal lamina and surface of the optic disk (hematoxylin and eosin, x 680). this, we speculate that if axoplasmic stasis is the basis for these drusen, stasis in axons other than those of ganglion cells (nerve fiber layer and optic disk axons) may also cause drusen. Ultrastructural studies of drusen of the optic nerve head associated with malignant melano ma were reported by Tso. 10 He postulated that extruded calcified mitochondria forms a nidus for calcium deposition which leads to the for mation of drusen. Puck, Tso, and Fishman 6 in their study of drusen of the optic nerve head associated with retinitis pigmentosa demon strated calcified and extruded mitochondria in the extracellular space in the vicinity of swollen axons and adjacent larger aggregations of calci fied drusen forming structures. Therefore, in our case, the presence of corpora amylacea in the lamina cribrosa and optic nerve is notewor thy. Since corpora amylacea appear to be degen erative enlargements of a glycoprotein-acid mucopolysaccharide complex found in the processes of fibrous astrocytes (or neuronal axons), 11 we speculate that dystrophic calcifica tion of this lesion may be a nidus for develop ment of the fully developed drusen. The ten dency toward calcification in this eye is further supported by the presence of calcification of the inner limiting lamina (Fig. 6) and the sever ity of the asteroid hyalosis (Fig. 2). Since dru sen of the optic disk are relatively common in retinitis pigmentosa as compared to the general population, 12 a predisposition to calcification of intraocular structures may be prevalent in this condition.
Vol. 103, No. 1
Optic Disk Drusen in Retinitis Pigmentosa
References 1. Robertson, D. M.: Hamartomas of the optic disk with retinitis pigmentosa. Am. J. Ophthalmol. 74:526, 1972. 2. DeBustros, S., Miller, N. R., Finkelstein, D., and Massof, R.: Bilateral astrocytic hamartomas of the optic nerveheads in retinitis pigmentosa. Retina 3:21, 1983. 3. Pillai, S., Limaye, S. R., and Saimovici, L. B.: Optic disk hamartoma associated with retinitis pig mentosa. Retina 3:24, 1983. 4. Hogan, M. J., and Zimmerman, L. E.: Ophthal mic Pathology. An Atlas and Textbook, ed. 2. Phila delphia, W. B. Saunders Co., 1962, pp. 580, 607-608. 5. Miiller, H.: Anatomische Beitrage zur Ophthalmologie. Graefes Arch. Ophthalmol. 4:1, 1858.
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6. Puck, A., Tso, M. O. M., and Fishman, G. A.: Drusen of the optic nerve associated with retinitis pigmentosa. Arch. Ophthalmol. 103:231, 1986. 7. Spencer, W. H.: Drusen of the optic disk and aberrant axoplasmic transport. Ophthalmologv 85:21, 1978. 8. Seitz, R., and Kersting, G.: Die Drusen der Sehnervenpapille und des Pigmentepithels. Klin. Monatsbl. Augenheilkd. 140:75, 1962. 9. Seitz, R.: Die intraocularen Drusen. Klin. Monatsbl. Augenheilkd. 152:203, 1968. 10. Tso, M. O. M.: Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmologv 88:1066, 1981. 11. Yanoff, M., and Fine, B. S.: Ocular Pathology. A Text and Atlas, ed. 2. Philadelphia, Harper and Row, 1982, p. 638. 12. Lorentzen, S. E.: Drusen of the Optic Disk. Copenhagen, Bogtrykkeriet Forum, 1966, p. 77.
To clarify the nature of mulberry-like excresences of the optic disk, we histopathologically studied the eye of a 66-year-old wom an with retinitis pigmentosa. Examination showed that the optic nerve excresences were ordinary drusen and not hamartomas. There was a marked predisposition to mineralization of other intraocular structures. THERE IS A continuing controversy concern ing the nature of the mulberry-like lesions of the optic disk in patients with retinitis pigmen tosa. Some investigators consider the lesions to be astrocytic hamartomas, while others have identified them as ordinary drusen of the optic disk. The present report, which is based on a pathologic study of an eye from a 66-year-old woman with retinitis pigmentosa, supports the conclusions of the two prior histopathologic investigations. The mulberry-like masses of the optic disk are drusen, not hamartomas. Our case also showed a marked predisposition to mineralization of other intraocular structures.
the family. The patient was legally blind by age 11 years and lost all light perception 15 years before her death. Two of her sisters became blind in their late 20s. The patient's only child, a daughter now in her late 30s, has normal vision. Two years before the patient's death, ophthalmoscopic examination of both eyes showed bone spicule pigmentation in the entire extramacular retina. There were attenuated retinal vessels and multiple small lesions over both optic nerves. Asteroid hyalosis was described in the vitreous. An electroretinogram per formed before loss of light perception was noted as "markedly abnormal" on medical re ports. The patient's eyes were enucleated within three hours of death. The right eye was used in an attempt to develop a cell culture line by the cell biology group at our institution. The left eye was fixed for gross pathology and study by light and electron microscopy. Reported here are the findings of the optic disk by light mi croscopy.
Case Report The patient, a 66-year-old woman, died of congestive heart failure. She had 11 siblings: four brothers and seven sisters. Three of her sisters developed retinitis pigmentosa al though there was no history of retinitis pig mentosa or other ocular disease in either side of
Accepted for publication Sept. 29, 1986. From the Jules Stein Eye Institute and the School of Medicine, University of California, Los Angeles. This study was supported in part by Public Health Service Center Grant EY 00331; National Eye Institute research grant EY 00725; Research Manpower Award (Dr. Foos), Research to Prevent Blindness, Inc.; Research Grant-inAid (Dr. Novack), National Society to Prevent Blind ness, New York; and research support (Dr. Novack), The Adler Foundation, Inc. Reprint requests to Robert Foos, M.D., Jules Stein Eye Institute, 800 Westwood Plaza, Los Angeles, CA 90024.
44
Fig. 1 (Novack and Foos). Gross section of the optic nerve head. A ring of yellow hyaline globules is seen at the outer margin of the optic disk and in parapapillary retina (x25).
©AMERICAN JOURNAL OF OPHTHALMOLOGY 103:44-47, JANUARY, 1987
Vol. 103, No. 1
Optic Disk Drusen in Retinitis Pigmentosa
45
Fig. 2 (Novack and Foos). Nasal and temporal calottes of the left eye. Dense asteroid hyalosis of the vitreous is seen (x3.4). The optic nerve measured 2 mm in length and was crushed. The left eye was opened vertically, temporal to the optic disk. The block containing the optic disk was washed, decalci fied for 24 hours in a solution of formic acid and sodium citrate, and processed for embedding in paraffin. The block was cut in 6-u.m sections and stained with hematoxylin and eosin. Rou tine stains were supplemented with periodic acid-Schiff reaction. On internal examination, dense spicular pig mentation was noted throughout the retina with relative sparing of the macula. The retinal vasculature was attenuated. A ring of yellow hyaline globules was seen at the margin of the optic disk and in the parapapillary retina (Fig. 1). There was dense asteroid hyalosis of the vitreous (Fig. 2). Light microscopy showed laminated acellular masses of different sizes and shapes located within the substance of the optic disk anterior to the scleral lamina cribrosa (Fig. 3), deep in the parapapillary retina (Fig. 4), and extruded
Fig. 4 (Novack and Foos). Light micrograph section shows a large laminated acellular parapapillary mass and two smaller masses of similar composition locat ed deep in the parapapillary retina. Calcification of the inner limiting lamina is also evident (arrow) (see Fig. 6) (hematoxylin and eosin, x 125).
Fig. 3 (Novack and Foos). Light micrograph section of the optic nerve and disk demonstrates laminated acellular masses of different sizes and shapes located within the substance of the optic disk, anterior to the scleral lamina cribrosa, and extruded from the optic disk and parapapillary retina (periodic acid-Schiff preparation, x 50). from the optic disk and parapapillary retina (Fig. 3). Corpora amylacea were present in the optic disk and the optic nerve (Fig. 5). In some areas, calcification of the inner limiting lamina was evident (Fig. 6). A string of mineralized deposits was seen lying under the basal lamina and surface of the optic disk (Fig. 7).
Discussion The nature of the lesions of the optic disk seen in retinitis pigmentosa have been widely discussed. Robertson 1 suggested that the mulberry-like masses seen on the optic nerve in retinitis pigmentosa were hamartomas. This
corpora amylacea present in the optic disk and optic nerve (arrows) (periodic acid-Schiff preparation, x 680).
46
AMERICAN JOURNAL OF OPHTHALMOLOGY
Fig. 6 (Novack and Foos). Light micrograph of calcified inner limiting lamina. Astrogliosis is also evident in the underlying optic disk (hematoxylin and eosin, x680). identification was made clinically and without histopathologic confirmation. His conclusions were supported by DeBustros and associates 2 and Pillai, Limaye, and Saimovici, 3 whose findings were also based on clinical studies. These studies suggested that the lesions are glial proliferations of hamartomas and not drusen. Hogan and Zimmerman 4 emphasized that both hamartomas and drusen are present in the optic disk. They described drusen of the optic disk as laminated acellular basophilic con cretions that are situated anterior to the lamina cribrosa and only infrequently reach the sur face of the nerve head. In contrast, optic disk hamartomas were described as calcifications and proliferations of astrocytic cells in the parapapillary retina.1-4 Our case is the third report of optic nerve head drusen associated with retinitis pigmentosa that has been studied histopathologically . 5 6 Miiller5 used drawings to illustrate lesions in the optic nerve head but not in the parapapillary retina. This supported the con clusion of Puck, Tso, and Fishman 6 that the drusen were ordinary and not astrocytic ham artomas as suggested previously. 1 ' 3 As in the report of Puck, Tso, and Fishman, the drusen in our specimen are largely in the more superficial aspect of the optic disk, but also involve the parapapillary retina at all lev els. Spencer, 7 Seitz and Kersting, 8 and Seitz9 propose that drusen of the optic disk are the end result of axonal degeneration. Based on
January, 1987
Fig. 7 (Novack and Foos). Light micrograph of the optic nerve head and parapapillary region shows a string of mineralized deposits underlying the basal lamina and surface of the optic disk (hematoxylin and eosin, x 680). this, we speculate that if axoplasmic stasis is the basis for these drusen, stasis in axons other than those of ganglion cells (nerve fiber layer and optic disk axons) may also cause drusen. Ultrastructural studies of drusen of the optic nerve head associated with malignant melano ma were reported by Tso. 10 He postulated that extruded calcified mitochondria forms a nidus for calcium deposition which leads to the for mation of drusen. Puck, Tso, and Fishman 6 in their study of drusen of the optic nerve head associated with retinitis pigmentosa demon strated calcified and extruded mitochondria in the extracellular space in the vicinity of swollen axons and adjacent larger aggregations of calci fied drusen forming structures. Therefore, in our case, the presence of corpora amylacea in the lamina cribrosa and optic nerve is notewor thy. Since corpora amylacea appear to be degen erative enlargements of a glycoprotein-acid mucopolysaccharide complex found in the processes of fibrous astrocytes (or neuronal axons), 11 we speculate that dystrophic calcifica tion of this lesion may be a nidus for develop ment of the fully developed drusen. The ten dency toward calcification in this eye is further supported by the presence of calcification of the inner limiting lamina (Fig. 6) and the sever ity of the asteroid hyalosis (Fig. 2). Since dru sen of the optic disk are relatively common in retinitis pigmentosa as compared to the general population, 12 a predisposition to calcification of intraocular structures may be prevalent in this condition.
Vol. 103, No. 1
Optic Disk Drusen in Retinitis Pigmentosa
References 1. Robertson, D. M.: Hamartomas of the optic disk with retinitis pigmentosa. Am. J. Ophthalmol. 74:526, 1972. 2. DeBustros, S., Miller, N. R., Finkelstein, D., and Massof, R.: Bilateral astrocytic hamartomas of the optic nerveheads in retinitis pigmentosa. Retina 3:21, 1983. 3. Pillai, S., Limaye, S. R., and Saimovici, L. B.: Optic disk hamartoma associated with retinitis pig mentosa. Retina 3:24, 1983. 4. Hogan, M. J., and Zimmerman, L. E.: Ophthal mic Pathology. An Atlas and Textbook, ed. 2. Phila delphia, W. B. Saunders Co., 1962, pp. 580, 607-608. 5. Miiller, H.: Anatomische Beitrage zur Ophthalmologie. Graefes Arch. Ophthalmol. 4:1, 1858.
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6. Puck, A., Tso, M. O. M., and Fishman, G. A.: Drusen of the optic nerve associated with retinitis pigmentosa. Arch. Ophthalmol. 103:231, 1986. 7. Spencer, W. H.: Drusen of the optic disk and aberrant axoplasmic transport. Ophthalmologv 85:21, 1978. 8. Seitz, R., and Kersting, G.: Die Drusen der Sehnervenpapille und des Pigmentepithels. Klin. Monatsbl. Augenheilkd. 140:75, 1962. 9. Seitz, R.: Die intraocularen Drusen. Klin. Monatsbl. Augenheilkd. 152:203, 1968. 10. Tso, M. O. M.: Pathology and pathogenesis of drusen of the optic nervehead. Ophthalmologv 88:1066, 1981. 11. Yanoff, M., and Fine, B. S.: Ocular Pathology. A Text and Atlas, ed. 2. Philadelphia, Harper and Row, 1982, p. 638. 12. Lorentzen, S. E.: Drusen of the Optic Disk. Copenhagen, Bogtrykkeriet Forum, 1966, p. 77.