T H E H I S T O P A T H O L O G Y O F P E T E R S ' ANOMALY CARL KUPFER, M.D.,
TOICHIRO KUWABARA, M.D.,
AND WALTER J. STARK,
M.D.
Bethesda, Maryland
Peters' anomaly belongs to that group of congenital defects associated with the devel opment of the anterior chamber. It is charac terized by corneal opacity, anterior synechiae, and often, glaucoma.1'2 Because of the sparse pathological material available for examination,s_T the pathogenesis of the glaucoma and corneal opacity is poorly understood. We report a case of Peters' anomaly, documented both by clinical examination and study of biopsy material. CASE REPORT A 23-month-old adopted boy of healthy Creole Indian parents was first referred to the Clinical Branch, National Eye Institute, in August 1972, with a diagnosis of bilateral congenital corneal opa cities, more marked on the right eye than the left eye. The patient was the product of an &x/i month pregnancy and had a birth weight of 2,240 g. The mother and father were said to have had no heredi tary disease. Examination indicated normal dermatoglyphic pattern, no digital abnormalities, a head circumfer ence in the 50th percentile, no hypertelorism, and an inner-outer canthus ratio of 0.35 (normal upper limit, 0.42). Results of systemic examination in cluding the cardiovascular system were normal. Under ketamine anesthesia, the horizontal and vertical corneal diameters were 11.2 X H-0 mm in the right eye and 11.8 X 11-5 mm in the left eye. Ultrasound measurements (A-scan) of the anteroposterior length in the right eye was 24 mm and 23.5 mm in the left eye. MacKay-Marg tonometry recorded an intraocular pressure in the right eye of 31 mm Hg, left eye 20 mm H g ; the intraocular pres sure in the right eye was confirmed by direct manometry using cannulation of the anterior chamber and measured 32 mm Hg. Tonography indicated an outflow facility in the right eye of 0.10 n l / m i n / m m H g with an intraocular pressure of 32 mm Hg, Schiotz, and in the left eye of 0.25 u.l/min/mm H g with an intraocular pressure of 17 mm Hg, Schiotz. On external examination of the right eye, there From the Clinical Branch (Drs. Kupfer and Stark), and the Laboratory of Vision Research (Dr. Kuwabara), National Eye Institute, Department of Health, Education, and Welfare, Bethesda, Mary land. Reprint requests to C. Kupfer, M.D., Building 31, Room 6A-03, National Institutes of Health, Be thesda, M D 20014.
was a pale white vascularized and edematous area in the cornea in the lower nasal quadrant, extending from the corneoscleral limbus into the pupillary space and occupying the full thickness of the cornea (Fig. 1). The left eye had a much smaller and less dense corneal opacity that was not vascularized. On gonioscopic examination of the right eye, processes from the iris collarette extended across the anterior cham ber to the corneal opacity. T h e angle was open 360 degrees but all angle structures were covered by heavy iris processes extending from the base of the iris onto the trabecular meshwork and onto Schwalbe's line. In the left eye, one iris process extended to the cornea at the site of the small opacity. The angle was open 360 degrees and ciliary body band, scleral spur, and trabecular meshwork were seen everywhere. There were few iris processes extend ing onto the trabecular meshwork and blood was seen in Schlemm's canal. On ophthalmologic exami nation of the right eye, the disk was elongated in the vertical meridian with slight cupping at the inferior pole. T h e cup/disk ratio was 0.6. In the left eye, the disk was round in appearance with a small cup, the cup/disk ratio being 0.1 to 0.2. T h e clinical impression was bilateral corneal opacities, more marked in the right eye and an angle abnor mality in the right eye with a congenital glaucoma and early cupping of the optic nerve head. The possibility of initial microphthalmus of the right eye with secondary increase in size of the globe due to increased intraocular pressure was considered be cause of the relatively smaller cornea but slightly larger globe on the right as compared to the left eye. At the time of the first admission, a trabeculectomy with iridectomy was performed on the right eye without control of the intraocular pressure. A second trabeculectomy was performed one month later with scarring of the filtering bleb. At the time of this second operation, it appeared that the iris was ad-
Fig. 1 (Kupfer, Kuwabara, and S t a r k ) . Right eye, vascularized and edematous corneal opacity.
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Fig. 3 (Kupfer, Kuwabara, and Stark). The scarred area of the corneal button. The stroma is highly cellular and vascularized. The pos terior surface is covered with extremely thin endothelium (hematoxylin-eosin, XlOO).
Fig. 2 (Kupfer, Kuwabara, and Stark). The area of the cornea to which iris tissue is adhering on the posterior surface is markedly edematous. Descemet's membrane is extremely thin (hematoxylineosin, XlOO). herent to the trabecular meshwork. Therefore, a cyclodiathermy of the right eye was performed after another month with adequate control of the intraocular pressure without medication. Accord ingly, a 7-mm penetrating keratoplasty of the right eye was performed the following year. RESULTS
Histopathology—The excised tissues from the first trabeculectomy and the subsequent corneal transplant were fixed in 4% glutaraldehyde in 0.15M phosphate buffer (pH 7.2) for about 15 minutes at room tempera ture, and were cut into small pieces after proper orientation. The pieces were postfixed in 1% osmium tetroxide in the same buffer solution, dehydrated in ethyl alcohol, and were embedded in an epoxy resin. Sec-
tions 1 (A thick were stained with toluidine blue for light microscopy. Ultrathin sections were stained with uranyl acetate and lead citrate and were examined by electron micro scopy. In some areas the iris from the first op eration, as well as from the corneal trans plant, adhered to the corneal endothelium or to trabecular meshwork. The corneal but ton was opaque in its entirety and in the area where iris tissue adhered, the stroma was markedly edematous (Fig. 2). The peripheral portion of the corneal specimen was vascularized and infiltrated (Fig. 3). The epithelium was irregular in its cellular arrangement and thickness, being detached from Bowman's membrane in several loca tions. The endothelium was not interrupted except at the area of the iris adhesion. How ever, the endothelial cells were extremely thin, measuring about 1 to 2 u. in thickness
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(Fig. 4, top). The cells seemed to join tightly and contained normal micro-organelles. Electronlucent areas, compatible with clusters of glycogen particles, were present in the matrix (Fig. 4, bottom). Descemet's membrane was
6SS
thin and its basal lamina substance was packed loosely (Figs. 4 and 5). Fine fibrils and collagen fibers were intermingled in the granular basal lamina substance. The appearance of Descemet's membrane was sim-
Fig. 4 (Kupfer, Kuwabara, and Stark). Top, The posterior portion of the cornea. The endothelium is thin. Poorly defined Descemet's membrane is indicated by arrows. AC indicates anterior chamber (X 8,700). Bottom, The endothelial cytoplasm contains normal microorganelles. Clusters of glycogen particles are unusual (arrows). Descemet's membrane is loosely built (x34,S00).
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Fig. 5 (Kupfer, Kuwabara, and Stark). Descemet's membrane with abundant electronlucent collagen fibers and fine filaments (X80.000).
ilar to that seen in embryonal stages of de velopment (Fig. 5). At the point where the iris tissue adhered to the loose connective tissue which had been formed posterior to Descemet's membrane, this connective tissue seemed to be continuous with that of the iris stroma (Fig. 6). In addition, pigmented iris cells formed a cluster at this point of adhesion. The posterior surface of the cornea adjacent to this point was covered with at tenuated endothelial cells, while the iris tissue facing the anterior chamber was covered with pigmented iris epithelium. The original thin Descemet's membrane was present 3 to S (x, anterior to the posterior surface. Also, a thin layer of abnormal Descemet's membrane was formed even more anterior to the original Descemet's membrane (Fig. 6). This pathological mem brane was interrupted in several locations. The specimen of trabecular meshwork and Schlemm's canal obtained at the time of
the first operation demonstrated changes more commonly seen in old age. These con sisted of the presence of abundant widebanded collagen fibers with a periodicity of 100 m[A (Fig. 7). Additionally, the endo thelial cells lining the trabecular beams con tained phagocytosed pigment granules. By comparison, the region of Schlemm's canal demonstrated normal endothelial cells lining the canal (Fig. 8). DISCUSSION
From a review of the histopathology of eyes in which there was no keratolenticular contact or cataract, it has been concluded that the most characteristic corneal feature of Peters' anomaly is the abnormality of both the Descemet's membrane and the endothelium in the area of the mrneal opacity and the thinning oj ?kg"r-f Ttqwmgn'c membrane.8"7 No electron microscopic ex amination of the region of the trabecular
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657
Fig. 6 (Kupfer, Kuwabara, and Stark). Area of the iridocorneal adhesion. The pigmented iris cells are surrounded by the basement membrane. Two layers of poorly defined Descemet's membranes are seen in the loose connective tissue (arrows). Extremely thin endothelial cells (En) are covering the posterior surface of the cornea. AC indicates anterior chamber (X 17,000).
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Fig. 7 (Kupfer, Kuwabara, and Stark). Trabecular meshwork showing the fine structure of the endothelial cells and a wide-banded collagen fibers (arrows). El indicates normal elastic fiber (X30,000). Bar gauge = 1.0 p.
Fig. 8 (Kupfer, Kuwabara, and Stark). Endothelium (En) of the Schlemm's canal is normal (x20,000). Bar gauge = 1 \i.
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meshwork and Schlemm's canal has been reported. In the present case, the corneal endothelial cells and Descemet's membrane although present in the region of the corneal opacity were abnormal in that the Descemet's membrane was immature in appearance and the endothelial cells were markedly attenu ated. Only at the point of iris adhesion were Descemet's membrane and endothelial cells absent. The original Descemet's membrane was buried within the loose connective tissue in the posterior portion of the swollen cor nea. Also, aberrant Descemet's membranes were found anterior to the original one. These findings suggest that the endothelial lining of the posterior surface of the cornea underwent loss in continuity on one or sev eral occasions during the course of the patho logical process. Although the denuded pos terior surface at the site of the adhesion was covered with iris tissue, fluid from the anterior chamber may have penetrated into the cornea easily at this site through the loose connective tissue of the iris and entered the cornea, causing the edema. Clinically, in the right eye, there were numerous iris processes adherent to trabecular meshwork. This eye had increased intraocular pressure and decreased outflow facility, suggesting that the abnormal mor phologic changes of the endothelium cover ing the trabecular beams might have allowed for iris processes to become adherent to them. Other pathological changes included wide-banded collagen and phagocytosed pig ment granules in the endothelial cells. All these changes are customarily inter preted as senile changes and, for a 2-year-old child, represent an accelerated aging process. With the involvement of the endothelial cells of the cornea and trabecular meshwork, the basic abnormality appears to be a failure in the normal differentiation of the mesoderm of the rim at the optic cup into normal endo thelial cells. However, an alternate hy pothesis is attractive. Recent work 8 indicated that naturally labeled quail neural crest cells transplanted into the neural crest region of
a stage-35 chick embryo become incorporated into corneal endothelium. Additionally, these qudil neural crest cells also become incorpo rated into trabecular endothelial cells (ac cording to a personal communication from M. C. Johnston and associates). In contrast, the vascular endothelium, including the lining of the counterpart of Schlemm's canal in the chick, is formed from mesoderm. This neural crest origin of corneal and trabecular endothelial cells in the chick may also hold for other species including man. Thus, Peters' anomaly may represent a failure of differentiation of neural crest cells destined for corneal and trabecular endothelium. Why do the corneal endothelial cells ap pear to be secreting such a Descemet's mem brane embryonal in nature? And why are the trabecular endothelial cells secreting a membrane containing wide-banded collagen and showing other signs of aging? One pos sibility may be that the trabecular endo thelium is more metabolically active than corneal endothelial cells with more rapid cell division as well as more rapid secretion of basement membrane. Thus, an abnormal corneal endothelium may secrete a sparse Descemet's membrane slowly while an ab normal trabecular endothelium may produce a rapidly aging membrane and shows evi dence of early aging or other regressive changes. SUMMARY
Corneal, iris, and trabecular meshwork tissue in a 23-month-old boy" with Peters' anomaly were studied with light and electron microscopy. In the cornea, both Descemet's membrane and endothelium were present beneath the area of the corneal opacity except at the point of iris adhesion. However, Des cemet's membrane was thin and embryonal in nature, and the endothelium markedly at tenuated. The trabecular meshwork demon strated changes characteristic of old age such as wide-banded collagen and the pres ence of phagocytosed pigment granules in the endothelium. The iris appeared normal
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except for anterior synechiae to the corneal opacity. Developmentally, the primary fault appeared to be a failure in the normal dif ferentiation of endothelial cells of the cornea and trabecular meshwork. ACKNOWLEDGMENT
Edwin Sheppard, M.D., referred this patient to the Clinical Branch, National Eye Institute. REFERENCES
1. Peters, A.: Ueber ageborene Defektbildung der Descemetschen Membran. Klin. Monatsbl. Augenheilkd. 44:27,105,1906. 2. Alkemede, P. P. H.: Dysgenesis Mesodermalis of the Iris and the Cornea. Assen, Royal Van Gorcum, 1969, pp. 83-98. 3. Towsend, W. M.: Congenital corneal leukomas. 1. Central defect in Descemet's membrane. Am. J. Ophthalmol. 77:80, 1974.
OCTOBER, 1975
4. Towsend, W. M., Font, R. L., and Zimmerman, L. E.: Congenital corneal leukomas. 2. Histopathologic findings in 19 eyes with central defect in Des cemet's membrane. Am. J. Ophthalmol. 77:192, 1974. 5. : Congenital corneal leukomas. 3. Histopathologic findings in 13 eyes with noncentral defect in Descemet's membrane. Am. J. Ophthalmol. 77: 400,1974. 6. Pouliquen, Y., Graf, B., and Saraux, H.: Etude histologique et ultrastructurale de la cornee dans deux cas de syndrome de Peters. Arch. Ophtalmol. 31:695, 1971. 7. Nakanishi, I., and Brown, S. I.: The histopathology and ultrastructure of congenital central corneal opacity (Peters' anomaly). Am. J. Ophthal mol. 72:801, 1971. 8. Johnston, M. C, Bhakdinaronk, A., and Reid, Y. C.: An expanded role for the neural crest in oral and pharyngeal development. In Bosma, J. F. (ed.) : Fourth Symposium on Oral Sensation and Percep tion. U.S. Government Printing Office, Washington, D.C., 1974, pp. 37-52.
TOICHIRO KUWABARA, M.D.,
AND WALTER J. STARK,
M.D.
Bethesda, Maryland
Peters' anomaly belongs to that group of congenital defects associated with the devel opment of the anterior chamber. It is charac terized by corneal opacity, anterior synechiae, and often, glaucoma.1'2 Because of the sparse pathological material available for examination,s_T the pathogenesis of the glaucoma and corneal opacity is poorly understood. We report a case of Peters' anomaly, documented both by clinical examination and study of biopsy material. CASE REPORT A 23-month-old adopted boy of healthy Creole Indian parents was first referred to the Clinical Branch, National Eye Institute, in August 1972, with a diagnosis of bilateral congenital corneal opa cities, more marked on the right eye than the left eye. The patient was the product of an &x/i month pregnancy and had a birth weight of 2,240 g. The mother and father were said to have had no heredi tary disease. Examination indicated normal dermatoglyphic pattern, no digital abnormalities, a head circumfer ence in the 50th percentile, no hypertelorism, and an inner-outer canthus ratio of 0.35 (normal upper limit, 0.42). Results of systemic examination in cluding the cardiovascular system were normal. Under ketamine anesthesia, the horizontal and vertical corneal diameters were 11.2 X H-0 mm in the right eye and 11.8 X 11-5 mm in the left eye. Ultrasound measurements (A-scan) of the anteroposterior length in the right eye was 24 mm and 23.5 mm in the left eye. MacKay-Marg tonometry recorded an intraocular pressure in the right eye of 31 mm Hg, left eye 20 mm H g ; the intraocular pres sure in the right eye was confirmed by direct manometry using cannulation of the anterior chamber and measured 32 mm Hg. Tonography indicated an outflow facility in the right eye of 0.10 n l / m i n / m m H g with an intraocular pressure of 32 mm Hg, Schiotz, and in the left eye of 0.25 u.l/min/mm H g with an intraocular pressure of 17 mm Hg, Schiotz. On external examination of the right eye, there From the Clinical Branch (Drs. Kupfer and Stark), and the Laboratory of Vision Research (Dr. Kuwabara), National Eye Institute, Department of Health, Education, and Welfare, Bethesda, Mary land. Reprint requests to C. Kupfer, M.D., Building 31, Room 6A-03, National Institutes of Health, Be thesda, M D 20014.
was a pale white vascularized and edematous area in the cornea in the lower nasal quadrant, extending from the corneoscleral limbus into the pupillary space and occupying the full thickness of the cornea (Fig. 1). The left eye had a much smaller and less dense corneal opacity that was not vascularized. On gonioscopic examination of the right eye, processes from the iris collarette extended across the anterior cham ber to the corneal opacity. T h e angle was open 360 degrees but all angle structures were covered by heavy iris processes extending from the base of the iris onto the trabecular meshwork and onto Schwalbe's line. In the left eye, one iris process extended to the cornea at the site of the small opacity. The angle was open 360 degrees and ciliary body band, scleral spur, and trabecular meshwork were seen everywhere. There were few iris processes extend ing onto the trabecular meshwork and blood was seen in Schlemm's canal. On ophthalmologic exami nation of the right eye, the disk was elongated in the vertical meridian with slight cupping at the inferior pole. T h e cup/disk ratio was 0.6. In the left eye, the disk was round in appearance with a small cup, the cup/disk ratio being 0.1 to 0.2. T h e clinical impression was bilateral corneal opacities, more marked in the right eye and an angle abnor mality in the right eye with a congenital glaucoma and early cupping of the optic nerve head. The possibility of initial microphthalmus of the right eye with secondary increase in size of the globe due to increased intraocular pressure was considered be cause of the relatively smaller cornea but slightly larger globe on the right as compared to the left eye. At the time of the first admission, a trabeculectomy with iridectomy was performed on the right eye without control of the intraocular pressure. A second trabeculectomy was performed one month later with scarring of the filtering bleb. At the time of this second operation, it appeared that the iris was ad-
Fig. 1 (Kupfer, Kuwabara, and S t a r k ) . Right eye, vascularized and edematous corneal opacity.
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OCTOBER, 1975
Fig. 3 (Kupfer, Kuwabara, and Stark). The scarred area of the corneal button. The stroma is highly cellular and vascularized. The pos terior surface is covered with extremely thin endothelium (hematoxylin-eosin, XlOO).
Fig. 2 (Kupfer, Kuwabara, and Stark). The area of the cornea to which iris tissue is adhering on the posterior surface is markedly edematous. Descemet's membrane is extremely thin (hematoxylineosin, XlOO). herent to the trabecular meshwork. Therefore, a cyclodiathermy of the right eye was performed after another month with adequate control of the intraocular pressure without medication. Accord ingly, a 7-mm penetrating keratoplasty of the right eye was performed the following year. RESULTS
Histopathology—The excised tissues from the first trabeculectomy and the subsequent corneal transplant were fixed in 4% glutaraldehyde in 0.15M phosphate buffer (pH 7.2) for about 15 minutes at room tempera ture, and were cut into small pieces after proper orientation. The pieces were postfixed in 1% osmium tetroxide in the same buffer solution, dehydrated in ethyl alcohol, and were embedded in an epoxy resin. Sec-
tions 1 (A thick were stained with toluidine blue for light microscopy. Ultrathin sections were stained with uranyl acetate and lead citrate and were examined by electron micro scopy. In some areas the iris from the first op eration, as well as from the corneal trans plant, adhered to the corneal endothelium or to trabecular meshwork. The corneal but ton was opaque in its entirety and in the area where iris tissue adhered, the stroma was markedly edematous (Fig. 2). The peripheral portion of the corneal specimen was vascularized and infiltrated (Fig. 3). The epithelium was irregular in its cellular arrangement and thickness, being detached from Bowman's membrane in several loca tions. The endothelium was not interrupted except at the area of the iris adhesion. How ever, the endothelial cells were extremely thin, measuring about 1 to 2 u. in thickness
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(Fig. 4, top). The cells seemed to join tightly and contained normal micro-organelles. Electronlucent areas, compatible with clusters of glycogen particles, were present in the matrix (Fig. 4, bottom). Descemet's membrane was
6SS
thin and its basal lamina substance was packed loosely (Figs. 4 and 5). Fine fibrils and collagen fibers were intermingled in the granular basal lamina substance. The appearance of Descemet's membrane was sim-
Fig. 4 (Kupfer, Kuwabara, and Stark). Top, The posterior portion of the cornea. The endothelium is thin. Poorly defined Descemet's membrane is indicated by arrows. AC indicates anterior chamber (X 8,700). Bottom, The endothelial cytoplasm contains normal microorganelles. Clusters of glycogen particles are unusual (arrows). Descemet's membrane is loosely built (x34,S00).
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Fig. 5 (Kupfer, Kuwabara, and Stark). Descemet's membrane with abundant electronlucent collagen fibers and fine filaments (X80.000).
ilar to that seen in embryonal stages of de velopment (Fig. 5). At the point where the iris tissue adhered to the loose connective tissue which had been formed posterior to Descemet's membrane, this connective tissue seemed to be continuous with that of the iris stroma (Fig. 6). In addition, pigmented iris cells formed a cluster at this point of adhesion. The posterior surface of the cornea adjacent to this point was covered with at tenuated endothelial cells, while the iris tissue facing the anterior chamber was covered with pigmented iris epithelium. The original thin Descemet's membrane was present 3 to S (x, anterior to the posterior surface. Also, a thin layer of abnormal Descemet's membrane was formed even more anterior to the original Descemet's membrane (Fig. 6). This pathological mem brane was interrupted in several locations. The specimen of trabecular meshwork and Schlemm's canal obtained at the time of
the first operation demonstrated changes more commonly seen in old age. These con sisted of the presence of abundant widebanded collagen fibers with a periodicity of 100 m[A (Fig. 7). Additionally, the endo thelial cells lining the trabecular beams con tained phagocytosed pigment granules. By comparison, the region of Schlemm's canal demonstrated normal endothelial cells lining the canal (Fig. 8). DISCUSSION
From a review of the histopathology of eyes in which there was no keratolenticular contact or cataract, it has been concluded that the most characteristic corneal feature of Peters' anomaly is the abnormality of both the Descemet's membrane and the endothelium in the area of the mrneal opacity and the thinning oj ?kg"r-f Ttqwmgn'c membrane.8"7 No electron microscopic ex amination of the region of the trabecular
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657
Fig. 6 (Kupfer, Kuwabara, and Stark). Area of the iridocorneal adhesion. The pigmented iris cells are surrounded by the basement membrane. Two layers of poorly defined Descemet's membranes are seen in the loose connective tissue (arrows). Extremely thin endothelial cells (En) are covering the posterior surface of the cornea. AC indicates anterior chamber (X 17,000).
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Fig. 7 (Kupfer, Kuwabara, and Stark). Trabecular meshwork showing the fine structure of the endothelial cells and a wide-banded collagen fibers (arrows). El indicates normal elastic fiber (X30,000). Bar gauge = 1.0 p.
Fig. 8 (Kupfer, Kuwabara, and Stark). Endothelium (En) of the Schlemm's canal is normal (x20,000). Bar gauge = 1 \i.
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meshwork and Schlemm's canal has been reported. In the present case, the corneal endothelial cells and Descemet's membrane although present in the region of the corneal opacity were abnormal in that the Descemet's membrane was immature in appearance and the endothelial cells were markedly attenu ated. Only at the point of iris adhesion were Descemet's membrane and endothelial cells absent. The original Descemet's membrane was buried within the loose connective tissue in the posterior portion of the swollen cor nea. Also, aberrant Descemet's membranes were found anterior to the original one. These findings suggest that the endothelial lining of the posterior surface of the cornea underwent loss in continuity on one or sev eral occasions during the course of the patho logical process. Although the denuded pos terior surface at the site of the adhesion was covered with iris tissue, fluid from the anterior chamber may have penetrated into the cornea easily at this site through the loose connective tissue of the iris and entered the cornea, causing the edema. Clinically, in the right eye, there were numerous iris processes adherent to trabecular meshwork. This eye had increased intraocular pressure and decreased outflow facility, suggesting that the abnormal mor phologic changes of the endothelium cover ing the trabecular beams might have allowed for iris processes to become adherent to them. Other pathological changes included wide-banded collagen and phagocytosed pig ment granules in the endothelial cells. All these changes are customarily inter preted as senile changes and, for a 2-year-old child, represent an accelerated aging process. With the involvement of the endothelial cells of the cornea and trabecular meshwork, the basic abnormality appears to be a failure in the normal differentiation of the mesoderm of the rim at the optic cup into normal endo thelial cells. However, an alternate hy pothesis is attractive. Recent work 8 indicated that naturally labeled quail neural crest cells transplanted into the neural crest region of
a stage-35 chick embryo become incorporated into corneal endothelium. Additionally, these qudil neural crest cells also become incorpo rated into trabecular endothelial cells (ac cording to a personal communication from M. C. Johnston and associates). In contrast, the vascular endothelium, including the lining of the counterpart of Schlemm's canal in the chick, is formed from mesoderm. This neural crest origin of corneal and trabecular endothelial cells in the chick may also hold for other species including man. Thus, Peters' anomaly may represent a failure of differentiation of neural crest cells destined for corneal and trabecular endothelium. Why do the corneal endothelial cells ap pear to be secreting such a Descemet's mem brane embryonal in nature? And why are the trabecular endothelial cells secreting a membrane containing wide-banded collagen and showing other signs of aging? One pos sibility may be that the trabecular endo thelium is more metabolically active than corneal endothelial cells with more rapid cell division as well as more rapid secretion of basement membrane. Thus, an abnormal corneal endothelium may secrete a sparse Descemet's membrane slowly while an ab normal trabecular endothelium may produce a rapidly aging membrane and shows evi dence of early aging or other regressive changes. SUMMARY
Corneal, iris, and trabecular meshwork tissue in a 23-month-old boy" with Peters' anomaly were studied with light and electron microscopy. In the cornea, both Descemet's membrane and endothelium were present beneath the area of the corneal opacity except at the point of iris adhesion. However, Des cemet's membrane was thin and embryonal in nature, and the endothelium markedly at tenuated. The trabecular meshwork demon strated changes characteristic of old age such as wide-banded collagen and the pres ence of phagocytosed pigment granules in the endothelium. The iris appeared normal
660
AMERICAN JOURNAL OF OPHTHALMOLOGY
except for anterior synechiae to the corneal opacity. Developmentally, the primary fault appeared to be a failure in the normal dif ferentiation of endothelial cells of the cornea and trabecular meshwork. ACKNOWLEDGMENT
Edwin Sheppard, M.D., referred this patient to the Clinical Branch, National Eye Institute. REFERENCES
1. Peters, A.: Ueber ageborene Defektbildung der Descemetschen Membran. Klin. Monatsbl. Augenheilkd. 44:27,105,1906. 2. Alkemede, P. P. H.: Dysgenesis Mesodermalis of the Iris and the Cornea. Assen, Royal Van Gorcum, 1969, pp. 83-98. 3. Towsend, W. M.: Congenital corneal leukomas. 1. Central defect in Descemet's membrane. Am. J. Ophthalmol. 77:80, 1974.
OCTOBER, 1975
4. Towsend, W. M., Font, R. L., and Zimmerman, L. E.: Congenital corneal leukomas. 2. Histopathologic findings in 19 eyes with central defect in Des cemet's membrane. Am. J. Ophthalmol. 77:192, 1974. 5. : Congenital corneal leukomas. 3. Histopathologic findings in 13 eyes with noncentral defect in Descemet's membrane. Am. J. Ophthalmol. 77: 400,1974. 6. Pouliquen, Y., Graf, B., and Saraux, H.: Etude histologique et ultrastructurale de la cornee dans deux cas de syndrome de Peters. Arch. Ophtalmol. 31:695, 1971. 7. Nakanishi, I., and Brown, S. I.: The histopathology and ultrastructure of congenital central corneal opacity (Peters' anomaly). Am. J. Ophthal mol. 72:801, 1971. 8. Johnston, M. C, Bhakdinaronk, A., and Reid, Y. C.: An expanded role for the neural crest in oral and pharyngeal development. In Bosma, J. F. (ed.) : Fourth Symposium on Oral Sensation and Percep tion. U.S. Government Printing Office, Washington, D.C., 1974, pp. 37-52.
