Journal of Pediatric Ophthalmology and Strabismus

Peripheral Peters' Anomaly: A Histopathologic Case Report

J A Fogle, MD; W R Green, MD; K R Kenyon, MD; S Naquin; J Gadol, MD

Abstract

Among the mesodermal dysgenses of the anterior segment,1'3 Peters' anomaly occurs as a congenital, central corneal leukoma overlying a defect of posterior stroma, Descemet's membrane and endothelium, and often associated with iris and lens adhesions to the margin of the corneal defect.4-9 The condition is usually bilateral and sporadic. Several etiologic possibilities have been proposed.10"12

From an infant with severe systemic abnormalities we have studied, by light and electron microscopy, both eyes in which congenital and symmetrical peripheral corneal opacities were associated with an iris coloboma in the same meridian. This case is an example of the secondary type of Peters' anomaly that develops following apposition of the lens to the cornea in contrast to either primary dysembryogenesis of the posterior cornea, or primary failure of lens vesicle separation.

CASE REPORT

This newborn infant was the product of the second pregnancy of a 24-year-old Negro woman. The mother's past medical history and the course of pregnancy were noncontributory. During the 37th week of gestation, spontaneous rupture of amnionic membranes occurred, labor was protracted over 24 hours, and was terminated by Caesarian section. The infant was apneic at delivery and required intubation. There was no hydramnios noted. In the Pediatric Intensive Care Unit, physical examination disclosed a head circumference of 46 cm, weight of 3,550 gm, and length of 50.5 cm. Vital signs included respiration, 60 per minute; pulse, 160 per minute; and temperature, 37.9 C. There were multiple malformations of the head, including hydrocephaly, enlarged anterior fontanelle, low-set ears, interiorly placed microphthalmic eyes with clouded corneas, malformed palate, and rudimentary nose with nostrils that lacked communication with the pharynx. Moro and suck reflexes were depressed.

Laboratory findings included: hematocrit, 42 percent; WBC count, 1 1,000; platelets, 320,000; reticulocytes, 13.8 percent. Chest roentgenogram and karyotype were normal.

Ophthalmologic examination disclosed absence of orbital rims and increased interpupillary distance of 62 mm. Inferonasal opacities occupied about onefourth of both corneas. Colobomatous defects of the iris were present subjacent to the corneal opacity in each eye, and the lens was apposed to the cornea in the area of opacity. Remnants of the tunica vasculosa lentis were evident. Tactile intraoculartensions were normal. A mild exotropia was noted. The media did not permit fundus examination.

Six hours after delivery the infant aspirated, developed bradycardia, and died. The eyes were enucleated six hours after death and fixed in glutaraldehyde-formalin.

Postmortem examination revealed bilateral absence of the frontal bones and partial absence of the temporal bones. Brain examination disclosed features of holopresencephaly with arhinencephaly and internal hydrocephalus from aqueductal stenosis or atresia.

Gross Examination

Both eyes were essentially the same and are described together. The globes were of normal size. The corneas measured 9x9 mm and were relatively clear except for opacification inferonasally (Fig. 1). The iris was absent subjacent to the area of corneal opacity, and in both eyes the inferonasal portion of the lens was juxtaposed to the area of corneal opacity. A small whitish plaque of tissue was present on the posterior surface of the lens inferonasally (Fig. 2).

Light Microscopic Examination

Both eyes had similar abnormalities of cornea, iris, lens, and angle as determined by study of serial sections.

The inferior nasal half of the cornea was about onehalf normal thickness in the area of lens apposition (Fig. 3), and superficial stromal vascularization was present in the peripheral one-third of the thinned area (Fig. 4). Bowman's membrane was absent in the area of vascularization (Fig. 4), was thickened in the remaining area of corneal thinning (Fig. 5), and was otherwise normal. In the thinned area, the stroma was irregular and hypercellular (Fig. 4);…

Among the mesodermal dysgenses of the anterior segment,1'3 Peters' anomaly occurs as a congenital, central corneal leukoma overlying a defect of posterior stroma, Descemet's membrane and endothelium, and often associated with iris and lens adhesions to the margin of the corneal defect.4-9 The condition is usually bilateral and sporadic. Several etiologic possibilities have been proposed.10"12

From an infant with severe systemic abnormalities we have studied, by light and electron microscopy, both eyes in which congenital and symmetrical peripheral corneal opacities were associated with an iris coloboma in the same meridian. This case is an example of the secondary type of Peters' anomaly that develops following apposition of the lens to the cornea in contrast to either primary dysembryogenesis of the posterior cornea, or primary failure of lens vesicle separation.

CASE REPORT

This newborn infant was the product of the second pregnancy of a 24-year-old Negro woman. The mother's past medical history and the course of pregnancy were noncontributory. During the 37th week of gestation, spontaneous rupture of amnionic membranes occurred, labor was protracted over 24 hours, and was terminated by Caesarian section. The infant was apneic at delivery and required intubation. There was no hydramnios noted. In the Pediatric Intensive Care Unit, physical examination disclosed a head circumference of 46 cm, weight of 3,550 gm, and length of 50.5 cm. Vital signs included respiration, 60 per minute; pulse, 160 per minute; and temperature, 37.9 C. There were multiple malformations of the head, including hydrocephaly, enlarged anterior fontanelle, low-set ears, interiorly placed microphthalmic eyes with clouded corneas, malformed palate, and rudimentary nose with nostrils that lacked communication with the pharynx. Moro and suck reflexes were depressed.

Laboratory findings included: hematocrit, 42 percent; WBC count, 1 1,000; platelets, 320,000; reticulocytes, 13.8 percent. Chest roentgenogram and karyotype were normal.

Ophthalmologic examination disclosed absence of orbital rims and increased interpupillary distance of 62 mm. Inferonasal opacities occupied about onefourth of both corneas. Colobomatous defects of the iris were present subjacent to the corneal opacity in each eye, and the lens was apposed to the cornea in the area of opacity. Remnants of the tunica vasculosa lentis were evident. Tactile intraoculartensions were normal. A mild exotropia was noted. The media did not permit fundus examination.

Six hours after delivery the infant aspirated, developed bradycardia, and died. The eyes were enucleated six hours after death and fixed in glutaraldehyde-formalin.

Postmortem examination revealed bilateral absence of the frontal bones and partial absence of the temporal bones. Brain examination disclosed features of holopresencephaly with arhinencephaly and internal hydrocephalus from aqueductal stenosis or atresia.

Gross Examination

Both eyes were essentially the same and are described together. The globes were of normal size. The corneas measured 9x9 mm and were relatively clear except for opacification inferonasally (Fig. 1). The iris was absent subjacent to the area of corneal opacity, and in both eyes the inferonasal portion of the lens was juxtaposed to the area of corneal opacity. A small whitish plaque of tissue was present on the posterior surface of the lens inferonasally (Fig. 2).

Light Microscopic Examination

Both eyes had similar abnormalities of cornea, iris, lens, and angle as determined by study of serial sections.

The inferior nasal half of the cornea was about onehalf normal thickness in the area of lens apposition (Fig. 3), and superficial stromal vascularization was present in the peripheral one-third of the thinned area (Fig. 4). Bowman's membrane was absent in the area of vascularization (Fig. 4), was thickened in the remaining area of corneal thinning (Fig. 5), and was otherwise normal. In the thinned area, the stroma was irregular and hypercellular (Fig. 4); the rudimentary, large, strap-like bands and irregularly branching keratocytes (Fig. 10, inset) contrasted with the normally precise lamellar organization elsewhere (Fig. 11, inset). Beyond the thinned area, including the extreme inferonasal periphery, Descemet's membrane was uniform in thickness (~ 2 microns; Figs. 6, 7, and 11 inset) and the endothelial cell layer was continuous. In the area of corneal thinning, however, Descemet's membrane became attenuated; and in the central zone of lens apposition, Descemet's membrane and the endothelium were absent (Figs. 4 and 10 inset). A thin layer of fibrous tissue was interposed between the attenuated Descemet's membrane and endothelium in the inferonasal periphery (Fig. 6). Thin delicate strands of residual tunica vasculosa lentis were present in both eyes. In the right eye these were less numerous and extended from the superior iris leaflet to attach to the cornea at the anterior margin of the thinned corneal area (Figs. 3 and 7). In the left eye these strands were more numerous, were attached to the anterior margin of the corneal lesion, and were also interposed between lens and cornea in some areas (Fig. 4).

The iris was totally absent inferiorly and nasally in the left eye (Fig. 8) and was present as a short stub in the right eye (Fig. 3).

The inferonasal portion of the lens was subluxed and apposed to the cornea. The lens capsule was intact and of normal thickness anteriorly, and the lens epithelium was normal except for occasional areas of mild proliferation at the point of contact with the cornea. There were also minor cataractous changes in the subjacent cortex. Dense fibrovascular tissue was adherent to the posterior surface of the lens inferonasally (Fig. 8), and had apparently induced wrinkling of the thickened lens capsule in the area of attachment (Fig. 9). Moderate cataractous changesincluding epithelial proliferation, some bladder-cell formation, disruption of cortical fibers and pockets of liquefaction - were present subjacent to this area. The fibrovascular tissue tapered inferiority and became continuous with the sclera in the region of the scleral roll (Fig. 9). Ciliary epithelium lined the posterior aspect of this fibrovascular tissue for a short distance, and vitreous strands and zonular fibers were attached to its peripheral and posterior aspects (Fig. 8).

Fig. 1. Gross photograph of right globe with inferonasal corneal leukoma (arrows).

Fig. 1. Gross photograph of right globe with inferonasal corneal leukoma (arrows).

Fig. 2. Interior of globe with superonasal cap removed. A white fibrous plaque (asterisk) is on the posterior lens surface nasally and extends through the iris coloboma to the region of the scleral spur (arrow). The inferonasal portion of the lens is subluxed forward.

Fig. 2. Interior of globe with superonasal cap removed. A white fibrous plaque (asterisk) is on the posterior lens surface nasally and extends through the iris coloboma to the region of the scleral spur (arrow). The inferonasal portion of the lens is subluxed forward.

Fig. 3. Histologic sections of anterior segment of right eye showing anterior subluxation of lens through nasal iris coloboma and touching the back of cornea. This zone of thinned cornea (large arrows) corresponds to the clinical leukoma. A remnant of the pupillary membrane (smaller arrows) bridges from temporal iris leaf to anterior edge of corneal defect. A fibrovascular plaque (arrowhead) is adherent to posterior surface of lens. Iris stub is encircled. (PAS. original magnification x 10)

Fig. 3. Histologic sections of anterior segment of right eye showing anterior subluxation of lens through nasal iris coloboma and touching the back of cornea. This zone of thinned cornea (large arrows) corresponds to the clinical leukoma. A remnant of the pupillary membrane (smaller arrows) bridges from temporal iris leaf to anterior edge of corneal defect. A fibrovascular plaque (arrowhead) is adherent to posterior surface of lens. Iris stub is encircled. (PAS. original magnification x 10)

Fig. 4. Thinned inferonasal cornea from left eye with disorganized stroma, absent Bowman's membrane in region of superficial vascularization (arrows), and remnant of pupillary membrane (arrowhead) interposed between lens and cornea. Descemet' s membrane and endothelium are absent in this area. The anterior lens capsule is uniform and intact. (Masson, original magnification x 240)

Fig. 4. Thinned inferonasal cornea from left eye with disorganized stroma, absent Bowman's membrane in region of superficial vascularization (arrows), and remnant of pupillary membrane (arrowhead) interposed between lens and cornea. Descemet' s membrane and endothelium are absent in this area. The anterior lens capsule is uniform and intact. (Masson, original magnification x 240)

Fig. 5. Thickened Bowman's membrane (asterisk) in region of thinned cornea without vascularization. (PAS, original magnification x 750)

Fig. 5. Thickened Bowman's membrane (asterisk) in region of thinned cornea without vascularization. (PAS, original magnification x 750)

Fig. 6. Fibrous tissue (asterisk) interposed between attenuated Descemet's membrane (arrows) and endothelium (arrowheads) in the inferonasal corneal periphery, adjacent to area of keratolenticular adhesion. (PAS, original magnification x 700)

Fig. 6. Fibrous tissue (asterisk) interposed between attenuated Descemet's membrane (arrows) and endothelium (arrowheads) in the inferonasal corneal periphery, adjacent to area of keratolenticular adhesion. (PAS, original magnification x 700)

Fig. 7. Thin strands of residual pupillary membrane (arrows) traceable to superior and temporal iris leaf, extending to anterior margin of keratolenticular apposition (arrowhead) of right eye. (PAS, original magnification x 250)

Fig. 7. Thin strands of residual pupillary membrane (arrows) traceable to superior and temporal iris leaf, extending to anterior margin of keratolenticular apposition (arrowhead) of right eye. (PAS, original magnification x 250)

Fig. 8. Left eye with total absence of iris inferonasally. A retrolenticularfibrovascular mass (asterisk) is adherent to lens capsule in region of iris coloboma. Vitreous strands and apparent zonular fibers extend from peripheral and posterior aspects of this mass (arrowheads), (hematoxylin and eosin. original magnification x 100)

Fig. 8. Left eye with total absence of iris inferonasally. A retrolenticularfibrovascular mass (asterisk) is adherent to lens capsule in region of iris coloboma. Vitreous strands and apparent zonular fibers extend from peripheral and posterior aspects of this mass (arrowheads), (hematoxylin and eosin. original magnification x 100)

Fig. 9. Serial sectioning shows that the fibrovascular retrolenticular tissue described in Fig. 8 has induced marked wrinkling (arrow) of posterior lens capsule. Inferiorly, the mass tapers and becomes continuous with sclera in region of the scleral spur, (hematoxylin and eosin, original magnification x 70)

Fig. 9. Serial sectioning shows that the fibrovascular retrolenticular tissue described in Fig. 8 has induced marked wrinkling (arrow) of posterior lens capsule. Inferiorly, the mass tapers and becomes continuous with sclera in region of the scleral spur, (hematoxylin and eosin, original magnification x 70)

Fig. 10. Inset shows stromal lamellae of corneal leukoma to be strap-like and loosely organized. Keratocytes are increased in number and have extended processes. Descemets membrane is absent. A discontinuous layer of similar-appearing cells fine the back of cornea, interposed among loose collagenous layers. Phase contrast, paraphenylenediamine, x 600. Main figure shows this area by electron microscopy to have randomly-oriented collagen fibrils and fibrob/astic-appearing cells with considerable rough-surfaced endoplasmic reticulum (original magnification x 12,500)

Fig. 10. Inset shows stromal lamellae of corneal leukoma to be strap-like and loosely organized. Keratocytes are increased in number and have extended processes. Descemets membrane is absent. A discontinuous layer of similar-appearing cells fine the back of cornea, interposed among loose collagenous layers. Phase contrast, paraphenylenediamine, x 600. Main figure shows this area by electron microscopy to have randomly-oriented collagen fibrils and fibrob/astic-appearing cells with considerable rough-surfaced endoplasmic reticulum (original magnification x 12,500)

In the area of the iris coloboma, the angle structures were also abnormal. The trabecular meshwork was either absent or rudimentary and no scleral spur couid be identified. The remaining structures of both eyes were not remarkable.

Electron Microscopic Examination

In the area of the corneal leukoma, stromal lamellae were poorly differentiated; the collagen fibrils seemed almost randomly oriented (Fig. 10). No Descemet's membrane-like material was discernible, and the cells lining the posterior aspect of the stroma appeared fibroblastic with an extensive array of rough-surfaced endoplasmic reticulum. The clinically-transparent regions of the stroma, however, showed relatively normal lamellarorganization, a uniform Descemet's membrane consisting of multilamellar basement membrane material with 1100 A banding, and a continuous endothelial monolayer (Fig. 1 1), At higher magnification (Fig. 12), striking differences were evident among the individual collagen fibrils: in clear cornea, fibrils of usual 240 A diameter were constant; but in the leukoma, collagen fibrils were consistently of larger diameter, ranging from 400 to 480 A, with many presumed elastic fibrils also present. The typical macroperiodicity of 600 A was apparent in the collagen fibrils of both areas.

Fig. 11. Inset shows the clinically-transparent area of stroma to have compact lamellae, fusiform keratocytes, uniform Descemet's membrane (2 µ thick), and continuous endothelial monolayer. Phase contrast, paraphenylenediamine, ? 500. Main figure shows these features by electron microscopy, including banded Descemet's membrane (bracketed) and endothelium with intact junctional complexes (circled) (original magnification x 6,000)

Fig. 11. Inset shows the clinically-transparent area of stroma to have compact lamellae, fusiform keratocytes, uniform Descemet's membrane (2 µ thick), and continuous endothelial monolayer. Phase contrast, paraphenylenediamine, ? 500. Main figure shows these features by electron microscopy, including banded Descemet's membrane (bracketed) and endothelium with intact junctional complexes (circled) (original magnification x 6,000)

Fig. 12. Higher magnification electron micrographs of stroma from clear area (above) and from area of leukoma (below); compare the consistent differences among the individual collagen fibrils. In clear cornea, fibrils of normal 240 A cross-sectional diameter are constant; whereas in the leukoma, collagen fibrils are of abnormally large diameter, ranging from 400 to 480 A, with increased numbers of elastic fibrils (E) (original magnification x 50,000)

Fig. 12. Higher magnification electron micrographs of stroma from clear area (above) and from area of leukoma (below); compare the consistent differences among the individual collagen fibrils. In clear cornea, fibrils of normal 240 A cross-sectional diameter are constant; whereas in the leukoma, collagen fibrils are of abnormally large diameter, ranging from 400 to 480 A, with increased numbers of elastic fibrils (E) (original magnification x 50,000)

DISCUSSION

The associations of corneal leukomas of several types with iris abnormalities, posterior embryotoxon, glaucoma, and cataract suggest a spectrum of developmental abnormalities of the anterior segment, among which Peters' anomaly is but one variant.1"3'13

Early theories about Peters' anomaly held that the corneal stromal opacity was secondary to inadequate separation of the lens vesicle10 or was a primary dysgenesis of the endothelium.11 Recent investigators have introduced the concept of corneal opacity on the basis of rnaldevelopment of other anterior segment structures with lens dislocation in some cases, giving rise to secondary keratolenticular adhesions, with resultant stromal opacity.5"7

Electron microscopic studies have disclosed associated and perhaps underlying abnormalities in collagen structures of the eye, particularly represented in Bowman's layer, stroma, and Descemet's membrane.7"9 In our case, the peripheral leukoma was characterized by absence of Bowman's layer with superficial vascularization, lamellar disorganization with collagen fibrils of remarkably large diameter, and no Descemet's membrane or endothelium. In the clinically unaffected areas of the cornea, the corresponding structures were normal. In congenital endothelial dystrophy, sclerocornea, and Peters' anomaly, these same associated features have often been linked to deranged endothelial function.13 It is unknown whether in most cases the stromal abnormalities represent additional primary defects in embryogenesis or are secondary to the endothelial defect.13

We consider the case reported here to be a secondary type of Peters' anomaly. There is histopathologic evidence from the complete and uniform lens capsule that the primary lens vesicle had entirely separated from the surface ectoderm. Subsequent apposition of the lens to the posterior cornea would then presumably have interfered with endothelial migration or destroyed preexisting endothelial cells in the abnormal area. The presence of the iris coloboma associated with retrolental fibrovascular tissue emanating from the region of the scleral spur, however, suggests dysgenesis of the iris and tertiary vitreous during the second and third months of gestation.14 Iris stroma and epithelium nasally do not develop properly in these cases, perhaps as a response to a prior or concurrent maldevelopment of tertiary vitreous. This situation can then permit the lens to sublux forward during embryogenesis of the cornea. The pupillary membrane can become involved in forward displacement of the lens and does not recede as it should. With continued keratolenticular contact, endothelial degeneration and corresponding corneal stromal edema with pannus formation might ensue. When lens apposition occurs before the third month, Descemet's membrane should not be evident even ultrastructurally.15 Thus, the presence of several embryologie abnormalities of the anterior segment in this case supports the interpretation that the corneal changes are probably secondary. In addition, these changes could not be consistently explained on the basis of either endothelial dysgenesis or faulty separation of the lens from the cornea. As with the studies reported by Townsend and coworkers4"6 and by Stone and coworkers,7 this case shows that Peters' anomaly is a more general term than originally considered.

Congenital corneal opacities may arise from various embryologie abnormalities, including failure of mesenchymal differentiation, faulty lens separation, and reapposition of lens and cornea in the developing eye.

SUMMARY

The clinical and pathologic findings of a case of congenital bilateral, peripheral corneal leukoma associated with iris coloboma and anterior subluxation of the lens are reported. The changes in the region of keratolenticular apposition include partial absence of Bowman's membrane, stromal vascularization and thinning with large-diameter collagen fibrils, and absence of Descemet's membrane and endothelium. The authors postulate that dysembryogenesis of the tertiary vitreous, with iris coloboma, resulted in apposition of the lens to cornea during the second and third month of gestation and that this apposition resulted in the observed peripheral corneal abnormalities.

REFERENCES

1 . Alkemade PPH: Dysgenesis mesodermalis of the iris and the cornea. Assen Royal Van Gorcum, 1969.

2. Reese AB, Ellsworth RM: The anterior chamber cleavage syndrome. Arch Ophthalmol 75:307, 1966.

3. Waring GO, Rodrigues MM, Laibson PR: Anterior chamber cleavage syndrome: A stepladder classification. Surv Ophthalmol 20:3, 1975.

4. Townsend WM: Congenital corneal leukomas. I. Central defect in Descemet's membrane. Am J Ophthalmol 77:80, 1974.

5. Townsend WM, Font RL, Zimmerman LE: Congenital corneal leukomas. 2. Histopathologic findings in 19 eyes with central defect in Descemet's membrane. Am J Ophthalmol 77:192, 1974.

6. Townsend WM, Font RL, Zimmerman LE: Congenital corneal leukomas. 3. Histopathologic findings in 13 eyes with noncentral defects in Descemet's membrane. Am J Ophthalmol 77:400, 1974.

7. Stone DL, Kenyon KR, Green WR, Ryan SJ: Congenital central corneal leukoma (Peters' anomaly). Am J Ophthalmol 81:173, 1976.

8. Nakanishi I, Brown SI: The histopathology and ultrastructure of congenital, central corneal opacity (Peters' anomaly). Am J Ophthalmol 72:801, 1971.

9. Pouliquen Y, Graf B, Saraux H et al: Etude histoíogique et ultra structura le de (a cornee dans deux cas de syndrome de Peters. Arch Ophtalmol (Paris) 31:675, 1971.

10. Peters A: Zur Frage der angeborenen Staphylome. Klin mbl f Augenheilk 76:803, 1926.

11. Seefelder R: Pathologish -anatomische Beiträge zur Frage der angeborenen zentralen Defektbildung der Hornhauthinterflache. Klin mbl Augenheilk 65:539, 1920.

12. Von Hippel E: Ueber Hydrophthalmus congenltus nebst Bermerkungen ueber die Verfä'rbung der Cornea durch Blutfarbstoff. Graefe Arch Ophthalmol 44:539, 1897.

1 3. Kenyon KR: Mesenchymal dysgenesis i? Peters' anomaly, sclerocornea and congenital endothelial dystrophy. Exp Eye Res 21:125, 1975.

14. Hogen MJ, Alvarado JA, Weddell JE: Histology of the Human Eye: An Atlas and Textbook. Philadelphia, WB Saunders Company, 1971, pp 204-205.

15. Wulle KG, Lershe W: Electron microscopic observations of the early development of the human corneal endothelium and Descemet's membrane. Ophthalmologica 157:451, 1969.

10.3928/0191-3913-19780301-04

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