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Intraocular Ossification and Hematopoiesis
INTRAOCULAR OSSIFICATION AND H E M A T O P O I E S I S ELLIOT M.
FINKELSTEIN,
M.D.
Boston, Massachusetts AND MILTON BONIUK,
M.D.
Houston, Texas TABLE 1
Intraocular bone formation has frequently been noted in pathologic specimens for many years and can no longer be considered un usual. However, the changes which accom pany it are less well known and, occasion ally, are unexpected. This paper describes a number of eyes with intraocular ossification and notes certain associated clinical and pathologic findings.
FACTORS INITIATING CHANGES LEADING TO ENUCLEATION
Primary Disease Injury (nonsurgical) Congenital deformity Recurrent iritis and keratitis Retinal detachment Surgical trauma Miscellaneous TOTAL
METHODS OF STUDY
From 1950 through February, 1966, 2,486 eyes were received by the Ophthalmic Pa thology Laboratory, Baylor University Col lege of Medicine. This study reviewed all eyes microscopically to determine if bone was present. The cases were grouped according to age, sex and race. The clinical histories were re viewed to determine the influence of various factors on bone formation. Particular atten tion was given ocular trauma, both acciden tal and surgical, and its time relationship to enucleation. At least one section from each specimen containing bone was examined mi croscopically, and notation was made of the type of bone, location, type of marrow and other associated pathologic changes. RESULTS
Of the 2,486 eyes studied, 119 (4.8%) had intraocular ossification; 79 (67%) were from men, 39 (32%) were from women From the Departments of Ophthalmology and Pathology, Baylor University College of Medicine, Houston. This study was supported by Grant 2T1 NB540S from the National Institute of Neurologi cal Diseases and Blindness. Reprint requests to Elliot M. Finkelstein, M.D., Beth Israel Hospital, 330 Brookline Avenue, Bos ton, Massachusetts 02215.
No. Cases 61 12 9 6 S 4 97
and, in one ( 1 % ) case, the sex was not spec ified. Of the 88 patients whose racial origin could be determined, 60 (68%) were Cauca sian, 25 (28%) were Negro, two (2%) were American Indian and one ( 1 % ) was Orien tal. Clinical information about the enucleated eye was available in 97 cases. Nonsurgical trauma, both perforating and nonperforating, the most frequent cause of the patho logic changes leading to enucleation, was present in 61 (63%) of these cases. Other initiating factors were congenital anomalies, inflammatory disease of unknown etiology and retinal detachment. There were five eyes which did poorly after intraocular surgery and nine eyes had been enucleated for mis cellaneous specified and unspecified reasons (table 1). The time interval between trauma and onset of disease and enucleation varied greatly (table 2 ) , ranging from two weeks to 78 years. In seven cases the interval was less than two years. All bone was calcified and lamellar in structure and was unifocal or multifocal. It was found (table 3) in all parts of the poste rior segment, lens, retina and in cyclitic
683
AMERICAN JOURNAL OF OPHTHALMOLOGY
684
TABLE 2 INTERVAL BETWEEN ONSET OF DISEASE OR TRAUMA AND ENUCLEATION
Interval (yr)
No. Cases
0-2 3-5 6-10 10 +
7 4 IS 69
TOTAL
95
membranes (figs. 1 and 2 ) . The most fre quent site was in the region of the pigment epithelium and the inner surface of the cho roid. The extent of osseous metaplasia in these eyes varied from small, peripapillary bone plaques (fig. 3) to large masses of cancellous bone which filled most of the poste rior segment. Fibrous metaplasia along the inner cho roid and proliferation of the pigment epithe lium (fig. 4-A), the most common changes adjacent to heterotopic bone, were present in most sections, regardless of the size of the lesion. In 35 (29.4%) cases, pigment was found within the bony spaces in the section studies (fig. 4-B). Other frequent findings were calcification of the retinal vessels (IS
OCTOBER, 1969
eyes) and cholesterol slits (21 eyes) (fig. 1B). Marrow was found within the heteroto pic bone in 82 (69%) of these eyes. Six (5%) cases had hematopoietic marrow (fig. 5) and 76 (64%) had fatty marrow (fig. 1B). DISCUSSION
Ossification within diseased or disorgan ized eyes has been recognized for many years and is similar to that found in other tissues. Duke-Elder 1 refers to four papers on intraocular ossification published more TABLE 3 SITES OF OSSIFICATION Site Posterior pole only Posterior pole to ora serrata Posterior pole and ora serrata Cyclitic membrane Peripapillary choroid Ora serrata Lens Retina Vitreous TOTAL
No. Cases 46 34 14 8 6 6 6 5 1 126*
* The total exceeds 119 since bone was present in multiple sites in some cases.
Fig. 1 (Finkelstein and Boniuk). (A) An eye which suffered trauma of unknown type 46 years prior to enucleation. The lens fibers have been replaced by calcified, lamellar bone with fatty marrow and cho lesterol slits. There is also ossification along the inner surface of the choroid. (Hematoxylin-eosin, X9.S.) (B) Temporal edge of lens with lamellar structure, fatty marrow (F) and cholesterol slits (arrows). (Hematoxylin-eosin, χ75.)
VOL. 68, NO. 4
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685
.9BSSÌ
Fig. 2 (Finkelstein and Boniuk). Ossified cyclitic membrane (arrows) of an eye which suffered a pene trating injury with scissors 20 years prior to enucleation. The totally detached retina lies behind the osse ous tissue. (Hematoxylin-eosin, XlO.S.)
than 100 years ago, among which was a re port by Hulke in 1857 providing the first proof that this represented true bone forma tion. The site most often involved in intraocu lar osseous metaplasia is the posterior pole (table 3). Duke-Elder suggests that an ade quate blood supply is necessary for ossifica tion of degenerating tissue and the vasculature of the posterior globe satisfies this pre requisite. However, a fibroblastic réponse also seems to be essential. In this study, al most every section with bone showed a fi broblastic response. Asbury,2 reported 23 cases, noted that all eyes in which bone was found had been severely injured or inflamed and that at least a minimal fibroblastic re sponse was present. Although fibrous meta plasia and an adequate blood supply appear
necessary for ossification, the stimulus for osteogenesis is still not understood. Moro 3 · 4 investigated osteogenesis of ocu lar tissues by injecting 95% alcohol into the vitreous and repeating the injection two months later. This led to ophthalmomalacia, fibrous changes and the development of com pact bone. He also implanted lens fibers, lens capsule and choroid beneath the skin of the ear ; bone formed only when uveal tissue was buried. He concluded that bone formation within the eye depends upon the osteogenic power of uveal tissue and the presence of fresh connective tissue which may act as a framework for bony tissues. In view of Moro's findings with trans planted lens material, it is interesting to note that, in reports on ossification within the human lens,5"7 there has always been a break
686
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1969
Fig. 3 (Finkelstein and Boniuk). Plaque of bone in the peripapillary choroid of an eye in which there was sudden onset of pain with visual loss 10 years prior to enucleation. Optic nerve (O) lies adjacent to the bone. (Hematoxylin-eosin, X43.S.) in the lens capsule and fibrous ingrowth prior to ossification. The terminology used to describe the bone seen in intraocular ossification is unclear. Billing and Ringertz 8 describe an ossifying fibroma as an acellular mass of tissue with mature bone spicules having a lamellar structure and a tendency to condense into compact bone but having no skeletal connec tion. These conditions are met in part by the heterotopic bone seen in this study. How
ever, other authorities, including Aegerter and Kirkpatrick,9 believe this term to be illdefined. Reed10 would probably consider the condition a type of complicated fibrous dysplasia, since the bone is lamellar and not of the woven "fiber" bone type. Most fascinating is the finding of hematopoietic marrow in several of these cases. Samuels11 found fatty marrow in many of 81 eyes with intraocular ossification but made no reference to finding hematopoietic
Fig. 4 (Finkelstein and Boniuk). (A) Pigment epithelium proliferation with adjacent areas of ossifica tion. (Hematoxylin-eosin, xS7.) (B) Proliferation of pigment epithelium within areas of compact bone. (Hematoxylin-eosin, X19S.)
688
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1969
Fig. S (Finkelstein and Boniuk). (A) Bone with hematopoietic marrow. (Hematoxylin-eosin, χ60.) (B) Hematopoietic cells under higher magnification. (Hematoxylin-eosin, X300.)
cells. Although most of our cases were simi lar to those Samuels described, we were sur prised to find six specimens with definite foci of hematopoietic marrow. It is logical to expect this finding when true bone is formed. Boch,12 in 1935, reported hematopoiesis within intraocular bone in an eye damaged by severe uveitis, presumably tuberculous. The failure of Samuels,11 Hagen and Ebel13 and Blatt14 to report hematopoiesis in any of the 136 eyes with ossification they stud ied indicates how infrequently this finding has been noted. Dubov15 found extramedullary hematopoiesis within one of four eyes with ossification studied microscopically. Bahn presented a similar case before the Southern Ophthalmic Pathology Club in 1964. Although intraosseous hematopoietic mar row within the eye has not received much attention, hematopoiesis itself has been well described. Reese and Biodi16 reported the presence of aggregations of hematopoietic
cells in the choroid of a number of autopsy specimens from infants who died during the neonatal period. They suggested that the vit reous haze seen in newborns might be due to hematopoietic cells and the uveal infiltration and fundus changes in myelogenous leuke mia might be in some part due to a resump tion of this fetal process. Our cases of he matopoietic marrow are probably not a re sponse to anemia since the pre-enucleation hemograms available in four of these six pa tients showed normal hemoglobin determina tions. Of the cases in which it was possible to determine the sex of the patient, males out numbered females 2 to 1. However, it is well known that vocational hazards and social customs make men more vulnerable to in jury. If cases due to trauma were eliminated, this difference would be much less marked. It seems reasonable to assume that bone for mation shows no predilection for either sex. Racial origin had no influence on ossifica-
VOL. 68, NO. 4
INTRAOCULAR OSSIFICATION
tion. Although approximately three times as many Caucasians as Negroes showed this change, the findings merely reflect the race distribution of specimens received at this laboratory. As already mentioned, trauma, both per forating and nonperforating, initiated the events which led to enucleation in 6 1 % of our cases (table 1). .Blatt found that 17 of 24 cases (71%) were secondary to perforat ing injuries, suggesting that massive intra ocular disorganization often follows trauma and subsequent fibrosis. Formation of bone within an eye usually occurs at least 10 to 12 years after the origi nal insult. Although Duke-Elder 1 states that
689
this is the usual interval, he reports one case in which bone was found 10 weeks after in jury. Those of our cases in which it was possi ble to estimate the interval between onset of ocular disease or time of injury and enucle ation showed that the average time elapsing was approximately 22 years; the interval was two years or less in seven cases and more than 10 years in 67 cases (table 2). That bone can form in an eye in a relatively short time is illustrated by a specimen from a two-year-old child who suffered a perforat ing wound of the cornea 10 months prior to enucleation. Ackerman17 found that bone was present
Fig. 6 (Finkelstein and Boniuk). (A) Choroidal melanoma that contained a small plaque of compact bone (area indicated by arrow). (Hematoxylin and eosin, X7.S.) (B) Plaque of compact bone (arrows) under higher magnification. (Hematoxylin-eosin, χ65.)
690
AMERICAN JOURNAL OF OPHTHALMOLOGY
in some cases of myositis ossificans within three to four weeks, although the absence of calcium in a lesion usually meant the injury occurred less than four to six weeks pre viously. Of our 119 cases, three had a his tory of ocular insult two months or less prior to enucleation. None of the eyes in the series contained malignant tumors; however, Reese18 men tions that Ewing reported a case of intraocu lar sarcoma originating in a focus of heterotopic ossification in an atrophie globe. Malig nant melanoma associated with intraocu lar ossification in an eye which had been blind from retinal detachment for 12 years was also mentioned. Since our study was completed, we have seen an eye with a choroidal melanoma that contained a small plaque of compact bone (fig. 6 ) . We also found calcification of the retinal vessels (15 eyes) and cholesterol deposits (21 eyes) in bone and other intraocular tis sues in our specimens, but these changes ap peared to be unrelated to the formation of bone. SUMMARY
A review of microscopic sections of 2,486 eyes submitted to the Ophthalmic Pathology Laboratory, Baylor University College of Medicine, from 1950 to early 1966, disclosed that 119 (4.8%) had intraocular ossification. The sex, race and age of patients under going enucleation and the factors initiating changes leading to enucleation have been dis cussed. In seven cases, the interval between insult and enucleation was two years or less. Bone formed 10 months after a perforating corneal wound in one two-year-old child. The inner surface of the choroid at the pos terior pole was the most frequent site of os sification. Other areas involved were the peri-
OCTOBER, 1969
papillary choroid, lens, vitreous and cyclitic membranes. Fatty marrow was found in 76 eyes and hematopoietic marrow in six. REFERENCES
1. Duke-Elder, W. S. : Textbook of Ophthalmol ogy. St. Louis, Mosby, 1941, v. 3, p. 2423. 2. Asbury, M. K. : Discussion of Samuels, B. Ossification of the choroid. Tr. Am. Acad. Ophth. Otolaryng: 43:241, 1938. 3. Moro, F. : Ricerche sperimentali sull'ossifica zione eterotopica endobulbare. Boll. Soc. Ital. Biol. Sper., 25:488, 1949. 4. : Ricerche sperimentali sull'ossificazione eterotopica endobulbare. Boll. Soc. Ital. Biol. Sper., 23:469, 1947. 5. Dunn, J. and Holden, W. A. : A case of ossifi cation of the lens, Arch. Ophth. 27:499, 1898. 6. Bellows, J. G. : Cataract and Anomalies of the Lens. St. Louis, Mosby, 1944, p. 399. 7. Samuels, B. : Cataract complicating corneal scars after perforating ulcers. Arch. Ophth. 29:583, 1943. 8. Billing, L. and Ringertz, N. : Fibro-osteoma. ActaRadiol. 27:129, 1946. 9. Aegerter, E. and Kirkpatrick, J. A., Jr. : Or thopedic Diseases. Philadelphia, Saunders, 1963. p. 486. 10. Reed, R. J. : Fibrous dysplasia of bone. Arch. Path. 75:480, 1963. 11. Samuels, B. : Ossification of the choroid. Tr. Am. Acad. Ophth. Otolaryng. 43 :193, 1938. 12. Bock, J. : Ueber einen Fall von hämatopoetischem Mark im heteroplastischen Knochen eines atrophischen Auges nebst Bemerkungen zum Sek tionsbefund bei Uveitis chronica. Z. Augenh. 86:257, 193S. 13. Hager, G. and Ebel, K. : Beitrag zur Intraokularen Knochenbildung (A contribution to intraocu lar ossification). Klin. Mbl. Augenh. 144:513, 1964. 14. Blatt, N. : Intraoculare Knochenbildungen : Osteom und Ossification. Arch. f. Ophth. 168 :220, 1965. 15. Dubov, S. : Intrabulbar ossification in cases of atrophie eyeball. Khirogiya (Sofia) 16:867, 1963. 16. Reese, A. B. and Biodi, F. C. : Hematopoieses in and around the eye. Am. J. Ophth. 38:214, 1954. 17. Ackerman, L. V.: Extra-osseous localized non-neoplastic bone and cartilage formation (socalled myositis ossificans). J. Bone Joint Surg. 40A :279, 1958. 18. Reese, A. B. : Tumors of the Eye. New York, Hoeber, 1963, ed. 2, p. 459.
FINKELSTEIN,
M.D.
Boston, Massachusetts AND MILTON BONIUK,
M.D.
Houston, Texas TABLE 1
Intraocular bone formation has frequently been noted in pathologic specimens for many years and can no longer be considered un usual. However, the changes which accom pany it are less well known and, occasion ally, are unexpected. This paper describes a number of eyes with intraocular ossification and notes certain associated clinical and pathologic findings.
FACTORS INITIATING CHANGES LEADING TO ENUCLEATION
Primary Disease Injury (nonsurgical) Congenital deformity Recurrent iritis and keratitis Retinal detachment Surgical trauma Miscellaneous TOTAL
METHODS OF STUDY
From 1950 through February, 1966, 2,486 eyes were received by the Ophthalmic Pa thology Laboratory, Baylor University Col lege of Medicine. This study reviewed all eyes microscopically to determine if bone was present. The cases were grouped according to age, sex and race. The clinical histories were re viewed to determine the influence of various factors on bone formation. Particular atten tion was given ocular trauma, both acciden tal and surgical, and its time relationship to enucleation. At least one section from each specimen containing bone was examined mi croscopically, and notation was made of the type of bone, location, type of marrow and other associated pathologic changes. RESULTS
Of the 2,486 eyes studied, 119 (4.8%) had intraocular ossification; 79 (67%) were from men, 39 (32%) were from women From the Departments of Ophthalmology and Pathology, Baylor University College of Medicine, Houston. This study was supported by Grant 2T1 NB540S from the National Institute of Neurologi cal Diseases and Blindness. Reprint requests to Elliot M. Finkelstein, M.D., Beth Israel Hospital, 330 Brookline Avenue, Bos ton, Massachusetts 02215.
No. Cases 61 12 9 6 S 4 97
and, in one ( 1 % ) case, the sex was not spec ified. Of the 88 patients whose racial origin could be determined, 60 (68%) were Cauca sian, 25 (28%) were Negro, two (2%) were American Indian and one ( 1 % ) was Orien tal. Clinical information about the enucleated eye was available in 97 cases. Nonsurgical trauma, both perforating and nonperforating, the most frequent cause of the patho logic changes leading to enucleation, was present in 61 (63%) of these cases. Other initiating factors were congenital anomalies, inflammatory disease of unknown etiology and retinal detachment. There were five eyes which did poorly after intraocular surgery and nine eyes had been enucleated for mis cellaneous specified and unspecified reasons (table 1). The time interval between trauma and onset of disease and enucleation varied greatly (table 2 ) , ranging from two weeks to 78 years. In seven cases the interval was less than two years. All bone was calcified and lamellar in structure and was unifocal or multifocal. It was found (table 3) in all parts of the poste rior segment, lens, retina and in cyclitic
683
AMERICAN JOURNAL OF OPHTHALMOLOGY
684
TABLE 2 INTERVAL BETWEEN ONSET OF DISEASE OR TRAUMA AND ENUCLEATION
Interval (yr)
No. Cases
0-2 3-5 6-10 10 +
7 4 IS 69
TOTAL
95
membranes (figs. 1 and 2 ) . The most fre quent site was in the region of the pigment epithelium and the inner surface of the cho roid. The extent of osseous metaplasia in these eyes varied from small, peripapillary bone plaques (fig. 3) to large masses of cancellous bone which filled most of the poste rior segment. Fibrous metaplasia along the inner cho roid and proliferation of the pigment epithe lium (fig. 4-A), the most common changes adjacent to heterotopic bone, were present in most sections, regardless of the size of the lesion. In 35 (29.4%) cases, pigment was found within the bony spaces in the section studies (fig. 4-B). Other frequent findings were calcification of the retinal vessels (IS
OCTOBER, 1969
eyes) and cholesterol slits (21 eyes) (fig. 1B). Marrow was found within the heteroto pic bone in 82 (69%) of these eyes. Six (5%) cases had hematopoietic marrow (fig. 5) and 76 (64%) had fatty marrow (fig. 1B). DISCUSSION
Ossification within diseased or disorgan ized eyes has been recognized for many years and is similar to that found in other tissues. Duke-Elder 1 refers to four papers on intraocular ossification published more TABLE 3 SITES OF OSSIFICATION Site Posterior pole only Posterior pole to ora serrata Posterior pole and ora serrata Cyclitic membrane Peripapillary choroid Ora serrata Lens Retina Vitreous TOTAL
No. Cases 46 34 14 8 6 6 6 5 1 126*
* The total exceeds 119 since bone was present in multiple sites in some cases.
Fig. 1 (Finkelstein and Boniuk). (A) An eye which suffered trauma of unknown type 46 years prior to enucleation. The lens fibers have been replaced by calcified, lamellar bone with fatty marrow and cho lesterol slits. There is also ossification along the inner surface of the choroid. (Hematoxylin-eosin, X9.S.) (B) Temporal edge of lens with lamellar structure, fatty marrow (F) and cholesterol slits (arrows). (Hematoxylin-eosin, χ75.)
VOL. 68, NO. 4
INTRAOCULAR OSSIFICATION
685
.9BSSÌ
Fig. 2 (Finkelstein and Boniuk). Ossified cyclitic membrane (arrows) of an eye which suffered a pene trating injury with scissors 20 years prior to enucleation. The totally detached retina lies behind the osse ous tissue. (Hematoxylin-eosin, XlO.S.)
than 100 years ago, among which was a re port by Hulke in 1857 providing the first proof that this represented true bone forma tion. The site most often involved in intraocu lar osseous metaplasia is the posterior pole (table 3). Duke-Elder suggests that an ade quate blood supply is necessary for ossifica tion of degenerating tissue and the vasculature of the posterior globe satisfies this pre requisite. However, a fibroblastic réponse also seems to be essential. In this study, al most every section with bone showed a fi broblastic response. Asbury,2 reported 23 cases, noted that all eyes in which bone was found had been severely injured or inflamed and that at least a minimal fibroblastic re sponse was present. Although fibrous meta plasia and an adequate blood supply appear
necessary for ossification, the stimulus for osteogenesis is still not understood. Moro 3 · 4 investigated osteogenesis of ocu lar tissues by injecting 95% alcohol into the vitreous and repeating the injection two months later. This led to ophthalmomalacia, fibrous changes and the development of com pact bone. He also implanted lens fibers, lens capsule and choroid beneath the skin of the ear ; bone formed only when uveal tissue was buried. He concluded that bone formation within the eye depends upon the osteogenic power of uveal tissue and the presence of fresh connective tissue which may act as a framework for bony tissues. In view of Moro's findings with trans planted lens material, it is interesting to note that, in reports on ossification within the human lens,5"7 there has always been a break
686
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1969
Fig. 3 (Finkelstein and Boniuk). Plaque of bone in the peripapillary choroid of an eye in which there was sudden onset of pain with visual loss 10 years prior to enucleation. Optic nerve (O) lies adjacent to the bone. (Hematoxylin-eosin, X43.S.) in the lens capsule and fibrous ingrowth prior to ossification. The terminology used to describe the bone seen in intraocular ossification is unclear. Billing and Ringertz 8 describe an ossifying fibroma as an acellular mass of tissue with mature bone spicules having a lamellar structure and a tendency to condense into compact bone but having no skeletal connec tion. These conditions are met in part by the heterotopic bone seen in this study. How
ever, other authorities, including Aegerter and Kirkpatrick,9 believe this term to be illdefined. Reed10 would probably consider the condition a type of complicated fibrous dysplasia, since the bone is lamellar and not of the woven "fiber" bone type. Most fascinating is the finding of hematopoietic marrow in several of these cases. Samuels11 found fatty marrow in many of 81 eyes with intraocular ossification but made no reference to finding hematopoietic
Fig. 4 (Finkelstein and Boniuk). (A) Pigment epithelium proliferation with adjacent areas of ossifica tion. (Hematoxylin-eosin, xS7.) (B) Proliferation of pigment epithelium within areas of compact bone. (Hematoxylin-eosin, X19S.)
688
AMERICAN JOURNAL OF OPHTHALMOLOGY
OCTOBER, 1969
Fig. S (Finkelstein and Boniuk). (A) Bone with hematopoietic marrow. (Hematoxylin-eosin, χ60.) (B) Hematopoietic cells under higher magnification. (Hematoxylin-eosin, X300.)
cells. Although most of our cases were simi lar to those Samuels described, we were sur prised to find six specimens with definite foci of hematopoietic marrow. It is logical to expect this finding when true bone is formed. Boch,12 in 1935, reported hematopoiesis within intraocular bone in an eye damaged by severe uveitis, presumably tuberculous. The failure of Samuels,11 Hagen and Ebel13 and Blatt14 to report hematopoiesis in any of the 136 eyes with ossification they stud ied indicates how infrequently this finding has been noted. Dubov15 found extramedullary hematopoiesis within one of four eyes with ossification studied microscopically. Bahn presented a similar case before the Southern Ophthalmic Pathology Club in 1964. Although intraosseous hematopoietic mar row within the eye has not received much attention, hematopoiesis itself has been well described. Reese and Biodi16 reported the presence of aggregations of hematopoietic
cells in the choroid of a number of autopsy specimens from infants who died during the neonatal period. They suggested that the vit reous haze seen in newborns might be due to hematopoietic cells and the uveal infiltration and fundus changes in myelogenous leuke mia might be in some part due to a resump tion of this fetal process. Our cases of he matopoietic marrow are probably not a re sponse to anemia since the pre-enucleation hemograms available in four of these six pa tients showed normal hemoglobin determina tions. Of the cases in which it was possible to determine the sex of the patient, males out numbered females 2 to 1. However, it is well known that vocational hazards and social customs make men more vulnerable to in jury. If cases due to trauma were eliminated, this difference would be much less marked. It seems reasonable to assume that bone for mation shows no predilection for either sex. Racial origin had no influence on ossifica-
VOL. 68, NO. 4
INTRAOCULAR OSSIFICATION
tion. Although approximately three times as many Caucasians as Negroes showed this change, the findings merely reflect the race distribution of specimens received at this laboratory. As already mentioned, trauma, both per forating and nonperforating, initiated the events which led to enucleation in 6 1 % of our cases (table 1). .Blatt found that 17 of 24 cases (71%) were secondary to perforat ing injuries, suggesting that massive intra ocular disorganization often follows trauma and subsequent fibrosis. Formation of bone within an eye usually occurs at least 10 to 12 years after the origi nal insult. Although Duke-Elder 1 states that
689
this is the usual interval, he reports one case in which bone was found 10 weeks after in jury. Those of our cases in which it was possi ble to estimate the interval between onset of ocular disease or time of injury and enucle ation showed that the average time elapsing was approximately 22 years; the interval was two years or less in seven cases and more than 10 years in 67 cases (table 2). That bone can form in an eye in a relatively short time is illustrated by a specimen from a two-year-old child who suffered a perforat ing wound of the cornea 10 months prior to enucleation. Ackerman17 found that bone was present
Fig. 6 (Finkelstein and Boniuk). (A) Choroidal melanoma that contained a small plaque of compact bone (area indicated by arrow). (Hematoxylin and eosin, X7.S.) (B) Plaque of compact bone (arrows) under higher magnification. (Hematoxylin-eosin, χ65.)
690
AMERICAN JOURNAL OF OPHTHALMOLOGY
in some cases of myositis ossificans within three to four weeks, although the absence of calcium in a lesion usually meant the injury occurred less than four to six weeks pre viously. Of our 119 cases, three had a his tory of ocular insult two months or less prior to enucleation. None of the eyes in the series contained malignant tumors; however, Reese18 men tions that Ewing reported a case of intraocu lar sarcoma originating in a focus of heterotopic ossification in an atrophie globe. Malig nant melanoma associated with intraocu lar ossification in an eye which had been blind from retinal detachment for 12 years was also mentioned. Since our study was completed, we have seen an eye with a choroidal melanoma that contained a small plaque of compact bone (fig. 6 ) . We also found calcification of the retinal vessels (15 eyes) and cholesterol deposits (21 eyes) in bone and other intraocular tis sues in our specimens, but these changes ap peared to be unrelated to the formation of bone. SUMMARY
A review of microscopic sections of 2,486 eyes submitted to the Ophthalmic Pathology Laboratory, Baylor University College of Medicine, from 1950 to early 1966, disclosed that 119 (4.8%) had intraocular ossification. The sex, race and age of patients under going enucleation and the factors initiating changes leading to enucleation have been dis cussed. In seven cases, the interval between insult and enucleation was two years or less. Bone formed 10 months after a perforating corneal wound in one two-year-old child. The inner surface of the choroid at the pos terior pole was the most frequent site of os sification. Other areas involved were the peri-
OCTOBER, 1969
papillary choroid, lens, vitreous and cyclitic membranes. Fatty marrow was found in 76 eyes and hematopoietic marrow in six. REFERENCES
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