Congenital Nonpigmented Epithelial Iris Cyst after Amniocentesis

Congenital Nonpigmented Epithelial Iris Cyst after Amniocentesis Clinicopathologic Report on Two Children Volker Rummelt, MD, Carmen Rummelt, Gottfried 0. H. Naumann, MD Background: Congenital nonpigmented epithelial iris cysts are not common. They may arise spontaneously from developmental entrapment of surface ectodermal epithelium or from occult ocular trauma prenatally or at birth. Patients and Methods: Between 1989 and 1991, an 8-month-old child and a 6year-old child presented with large, progressive congenital epithelial iris cysts. Both children had a maternal history of diagnostic amniocentesis after an ultrasound scan, and there was no history of postnatal ocular trauma. The cysts were successfully removed by a modified block excision and tectonic corneoscleral grafting. Results: A dense adherence of the cyst wall to Descemet's membrane resembled old anterior synechiae after occult perforation of the globe in both patients. On histopathologic examination, the epithelial lining of the cysts consisted of non-keratinizing stratified squamous epithelium with goblet cells resembling conjunctival epithelium. A perforating limbal scar with a corresponding break in Descemet's membrane could be detected in one eye. The long-term visual acuity of both children was encouraging, and there was no evidence of recurrence of the iris cyst during the follow-up period (average, 23 months). Conclusions: The authors conclude that the clinical and histopathologic features of these congenital iris cysts may be consistent with an occult intrauterine limbal perforation of the anterior chamber with a needle during amniocentesis. Amniocentesis, when not guided by a real-time ultrasound scan, may be a risk factor for prenatal ocular trauma, which should be considered in the differential diagnosis of congenital ocular disorders. Ophthalmology 1993;100:776-781

Transabdominal midtrimester amniocentesis and chorionic villus samplings currently are indispensable diagOriginally received: September 21, 1992. Revision accepted: December 15, 1992. From the Department of Ophthalmology, University ofErlangen-Niirnberg, Erlangen, Germany. Dr. Volker Rummelt is currently affiliated with F. C. Blodi Eye Pathology Laboratory, Department of Ophthalmology, University of Iowa, Iowa City. Presented as a poster at the American Academy of Ophthalmology Annual Meeting, Anaheim, October 1991. Supported in part by grant Ru 464/3-1 of the Deutsche Forschungsgemeinschaft, Germany (Dr. Rummelt). Reprint requests to Volker Rummelt, MD, Department of Ophthalmology, University ofErlangen-Niirnberg, Schwabachanlage 6, D-8520 Erlangen, Germany.

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nostic tools for prenatal evaluation of genetic and other congenital disorders of the fetus (Fig 1). Midtrimester amniocentesis bears only a low rate of fetal and maternal complications if controlled or even guided by a real-time ultrasound scan. 1 Despite the recognized safety of this invasive procedure, fetal injuries occur in an estimated 2% to 4% of the cases?-5 Most are innocuous injuries to the skin, 5 but fetal ocular complications also have been reported sporadically. 6- 12 Cross and Maumenee 12 described a patient with a congenital epithelial iris cyst, which occurred after a presumed perforating ocular trauma during midtrimester amniocentesis. These congenital nonpigmented epithelial iris cysts are rare unilateral tumors of the anterior uvea, usually presenting at birth or the first few months oflife.U- 15 They may arise spontaneously from developmental entrapment of surface ectoderm during the time of the lens vesicle

Rummelt et al · Iris Cysts and Amniocentesis

Figure 1. Transabdominal midtrimester amniocentesis guided by realtime ultrasound scanning. H = head of the fetus; arrows = amniocentesis needle. (Courtesy of Dr. H. J. Voigt, Department of Gynecology and Obstetrics, University of Erlangen-Niirnberg, Erlangen, Germany.)

formation 16•17 or after an occult ocular trauma prenatally 12 or at birth. 13• 18 •19 These acquired epithelial ingrowth cysts are known to arise from implanted surface epithelium (corneal, limbal, conjunctival)_2°-22 Spontaneous congenital iris cysts cannot be differentiated clinically or histopathologically from a congenital epithelial ingrowth cyst after trauma unless a fistula or scar is present, indicating a previous perforating injury to the globe. However, a clinical history of a presumed intrauterine ocular injury may help to distinguish between both forms. 20•21 We report on the clinical and histopathologic features of two children with large progressive congenital epithelial iris cysts after a presumed intrauterine trauma during diagnostic amniocentesis. The cysts were successfully removed by a modified block excision and tectonic corneoscleral grafting. 21 •22

Case Reports Case 1. A white Yugoslavian boy was born on November I,

1988, as the first child to a healthy 39-year-old woman. The pregnancy and delivery were normal. A transabdominal amniocentesis was performed in the eighteenth gestational week directly after an ultrasound scan of the fetus and the placenta, as a routine procedure because ofthe advanced maternal age. Results of examination of the amniotic fluid demonstrated a normal chromosomal rate. Results of routine examination on the first day oflife showed a normal healthy baby except for a cystic mass in the anterior chamber of his right eye. At 8 months of age, first examination at our hospital (July 1989) was performed with the baby under general anesthesia. The left eye was normal. The right eye showed a large epithelial iris cyst extending from the 3:30-o'clock to the ?-o'clock position, occupying nearly half of the pupil (Fig 2). The cyst involved the posterior corneal surface and the chamber angle structures gonioscopically. The clear cornea of both eyes measured 11.5 X 11.5 mm, the axial length of the globes was 19.2 mm measured by ultrasound, and the intraocular pressure

was lO mmHg in both eyes measured by applanation tonometry. The lens appeared clear and the posterior pole was normal with no evidence of glaucomatous cupping of the optic disc. Because there was a documented growth of the epithelial cyst, which impinged on the visual axis, the cyst was excised with a modified block excision of 8.2 mm in diameter. The resulting defect was covered with a tectonic corneoscleral graft 8.2 mm in diameter. The postoperative course was uneventful. At the last examination in February 1992, the cornea remained clear, the graft was opaque and partly vascularized. The lens showed an early posterior subcapsular cataract. Visual acuity of his right eye was encouraging because the child tolerated occlusion of his fellow eye without problems, grasping at very small objects steadily. The intraocular pressure was normal. Histopathologic Findings. The en bloc-excised tissue, consisting of one-fourth cornea and three-fourths sclera, iris, and pars plicata of the ciliary body with the adjacent epithelial cyst, measured 8.2 X 3.5 mm. The collapsed congenital nonpigmented epithelial iris cyst extending from the posterior corneal surface to the iris root consisted of two or three layers of nonkeratinizing stratified squamous epithelium with goblet cells (Fig 3A). The chamber angle and the anterior surface of the pars plicata of the ciliary body were not involved. The free margins of the cyst almost were entirely surrounded by uveal tissue. There was a tight connection between the surface of the cyst and Descemet's membrane, where corneal endothelial cells proliferated on the cyst wall (Figs 3B and 3C). The lumen of the cyst was partly filled with mucinous material. A break in Descemet's membrane with round edges was present in the peripheral cornea (Fig 3C) and could be identified in 65 serial sections (3 Jim each) of the entire tissue.

Case 2. A white girl was born on October 17, 1984, as the first child of healthy parents. The pregnancy and delivery were normal. In the forty-third week of gestation, a transvaginal amnioscopy followed by amniocentesis was performed three times after an ultrasound scan because the mother had carried the baby 3 weeks beyond term. Results of examination ofthe bloodstained amniotic fluid showed fetal blood. Results ofthe routine examination on the first day of life showed a normal healthy baby. At 5 years of age, a progressively enlarging epithelial iris cyst of her left eye was noted by the parents. There was no history of postnatal ocular trauma. The cyst was treated at another institution with a neodymium:YAG laser photocoagulation twice without success. Two months later, on the first examination at our hospital (January 1991), the girl had a large epithelial iris cyst extending from the 5- to ?-o'clock position, occupying nearly half of the pupil (Fig 4A). The posterior corneal surface and the chamber angle structures were involved gonioscopically (Fig 4B). The cyst wall was partly vascularized. The clear cornea measured 11.5 X 11.5 mm, visual acuity was 20/50 in the left eye and 20/ 20 in the right, and the intraocular pressure was 14 mmHg in both eyes as measured by applanation tonometry. The lens was clear except for a circumscribed posterior synechiae and the posterior pole was normal without evidence of glaucomatous cupping of the optic disc. Because there was documented growth of the cyst, which impinged on the visual axis, the cyst was removed by a modified block excision 7.3 mm in diameter. The resulting defect was covered with a tectonic corneoscleral graft 7.5 mm in diameter. The postoperative course was uneventful. At the last examination in April 1992, visual acuity was 20/20 in the left eye, and intraocular pressure was 14 mmHg. The cornea and the lens remained clear (Fig 4C). Histopathologic Findings. The en bloc-excised tissue, consisting of one-fourth cornea and three-fourths sclera, pars

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Top left, Figure 2. Intraoperative clinical picture Ganuary 1989) of the right eye with a congenital nonpigmented epithelial iris cyst occupying nearly half of the anterior chamber. Figure 3. Case 1. A, second row left, histologic features of congenital nonpigmented epithelial iris cyst (periodic acid-Schiff stain). C = cornea; S = sclera; Cb = ciliary body; CY = collapsed nonpigmented epithelial iris cyst; I = iris (original magnification, X16). B, third row left, two to three layers of nonkeratinizing stratified squamous epithelium with goblet cells cover the posterior corneal surface. Corneal endothelial cells proliferate on the surface of the cyst wall (arrows), producing a dense adhesion of the cyst to Descemet's membrane (original magnification, X240). C, bottom left, break in Descemet's membrane with round edges (arrows) 180 J
Rummelt et al · Iris Cysts and Amniocentesis plicata of the ciliary body, and iris with the adjacent epithelial cyst, measured 7.3 X 3.0 mm. The collapsed congenital nonpigmented epithelial iris cyst extended from the posterior corneal surface over the chamber angle structures and the anterior surface of the ciliary body onto the iris surface (Figs SA and 5B). The epithelial lining consisted of nonkeratinizing stratified squamous epithelium with scattered goblet cells. The cyst was almost totally surrounded by uveal tissue. Corneal endothelial cells had proliferated secondarily on this uveal tissue, covering the cyst wall (Figs 5C and 5D). Incisions in the limbal region were performed intraoperatively to drain the cyst's content and to reduce its diameter. A break in Descemet's membrane could not be identified.

Scanning electron microscopy (CAM SCAN, Series 4, Cambridge, UK) demonstrated the tight connection of the cyst with the posterior corneal surface and the chamber angle structures. The invaded epithelium consisted of uniform polygonal cells with well-defined cell borders, apical microvilli, and occasional goblet cells with mucinous droplets (Fig 5E).

Comment The presence of a nonpigmented epithelial iris cyst at birth or during the early neonatal period (Figs 2 and 4A) strongly suggests a congenital abnormality (see case 1). 7 •12

s Cb '

Figure 5. Case 2. A, top left, histologic features of congenital nonpigmented epithelial iris cyst (periodic acid-Schiff stain). C = cornea; S = sclera; Cb = ciliary body; I = iris; arrows = intraoperative transcorneal stab incision in the limbal region; asterisks = lumen of the collapsed iris cyst (original magnification, Xl6). B, center left, two or three layers of nonkeratinizing stratified squamous epithelium cover the chamber angle structures and the anterior surface of the ciliary body. C = cornea; CY = epithelial iris cyst; S = sclera; arrows = Schlemm's canal (original magnification, X 120). C, bottom left, a few goblet cells can be found in the cyst wall (original magnification, Xl20). D, top right, corneal endothelial cells (arrows) proliferate on uveal tissue surrounding the cyst (original magnification, X240). E, bottom right, scanning electron microscopy of the epithelial lining of the cyst consisting of epithelial cells with well-defined cell borders, apical microvilli, and mucinous droplets indicating conjunctiva.

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Ophthalmology

Volume 100, Number 5, May 1993

However, a delayed clinical appearance of the epithelial cyst also would be consistent with a congenital origin, because of the slow-growing character of some of these cysts (see case 2). 21 Their growth pattern may be dependent on the structure of their epithelial lining and the presence or absence of a secondary proliferation of corneal endothelial cells on their wall. A cyst consisting of stratified squamous epithelium with goblet cells resembling conjunctival epithelium usually tends to enlarge progressively due to the continuous production of mucin. In contrast, cysts without any evidence of goblet cells within their epithelial lining usually are stable for a long period. Corneal endothelial cells proliferating secondarily on the outer surface of the cyst wall form a net-like structure, which then may retard the expansion of the cyst. This mechanism may be the cause of the very slow-growing character of some of these cysts. 15 Congenital epithelial iris cysts of a presumed spontaneous origin have been reported sporadically. 13- 15 The histopathogenesis of these cysts is still not clear in detail. Proposed mechanisms include developmental entrapment of surface ectoderm, 14- 25 neuroectoderm, 26 - 29 or mesoderm 30- 31 during the lens vesicle formation. The presence of goblet cells within the epithelial lining of the cyst seems to establish surface ectodermal epithelium as cellular origin of those cases. These spontaneous congenital nonpigmented epithelial iris cysts cannot be differentiated clinically or histopathologically (Figs 3A and SA) from posttraumatic epithelial ingrowth cysts of the anterior chamber, unless a fistula or a limbal or corneal scar is present. The epithelial ingrowth cysts are known to arise from implanted surface epithelium after a perforating injury or anterior segment surgery. 19- 22•32 The clinical history of a presumed prenatal ocular injury (i.e., amniocentesis) or trauma at birth helps to distinguish clinically between a spontaneous and an acquired origin of congenital iris cysts. The presumed posttraumatic intrauterine nature of the cysts in our patients seems plausible because there was ( 1) a history of amniocentesis, (2) no history of postnatal ocular trauma, although this never can be completely excluded, and (3) a dense adherence of the cyst wall to the posterior corneal surface. These anterior synechiae (Figs 3B and 50) would be consistent with an old covered perforation of the anterior chamber occurring at the limbus where the spontaneous repair of the conjunctival wound subsequently obscured the corneoscleral scar. 7•12 In addition, the detection of (I) goblet cells within the epithelial lining of both cysts resembling conjunctival epithelium and (2) a limbal scar in the excised tissue (case I) with a corresponding break in Descemet's membrane (Fig 3C) with round edges and a width of approximately I80 ~m may be consistent with a perforation of the globe by the tip of an amniocentesis needle of I 50 to 200 ~m in diameter. Clusters of corneal, limbal, or conjunctival epithelial cells could be spread into the eye by the needle during this procedure. Perforation of the globe before the sixteenth or eighteenth week of gestation injures an eye of 3 to 4 mm in diameter. Although ocular trauma to the fetus during the first or the second trimester may cause serious functional damage or gross malformations because

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organogenesis is incomplete, small injuries to the limbal region may not necessarily produce large defects, which may heal without serious complications. 8•11 Many nonsurgical and surgical techniques for the treatment of these potentially blinding lesions have been devised. 15 •18 - 22 Because the purpose of every treatment must be the complete eradication of the epithelium to avoid recurrences or conversion of cystic to diffuse sheetlike epithelial ingrowth, the treatment of choice for these nonpigmented epithelial iris cysts currently is a block excision of the cyst together with the adjacent iris, the full thickness cornea and sclera, and the pars plicata of the ciliary body, as described previously. 15 •20- 22 The resulting defect is covered with a tectonic corneoscleral graft. Using this technique, direct manipulation of the very delicate cyst wall, which often consists of not more than two or three layers of stratified squamous epithelium, is avoided, and the cyst epithelium is completely excised. During the follow-up period (average, 23 months), no recurrence of the iris cysts was noted clinically. The transabdominal and the transvaginal amniocenteses in our patients' history were performed by a gynecologist immediately after an ultrasound scan. Although a routine midtrimester amniocentesis bears only a low risk of fetal and maternal complications, 2- 5 serious injuries to the heart, lungs, brain, and the limbs of the fetus, resulting in loss of a limb, have been reported. 5 Ocular trauma is rare. Only a few previous reports6- 12 related congenital ocular abnormalities to a presumed intrauterine trauma during amniocentesis. Amniocentesis can be performed directly after an ultrasound scan of the placenta and the fetus ("controlled amniocentesis") and during a real-time ultrasound scan ("guided amniocentesis"), guiding the needle into the pool of amniotic fluid under visual control. Gynecologists should be advised to direct their needles away from the fetus, especially its head and limbs, which are the most vulnerable structures (Fig 1). However, it is impossible to avoid all the injuries to the fetus, because sudden and strong movements of the fetus may aim the needle directly to the fetus instead of to a pool of amniotic fluid. If amniocentesis always is performed under realtime ultrasound scanning to detect sudden fetal movements, the rate of complications may be further decreased or eliminated. 7 So far, unguided or even uncontrolled amniocentesis may be a risk factor for prenatal ocular trauma, which should be considered in the differential diagnosis of congenital ocular disorders.

References 1. Milunsky A. Risk of amniocentesis for prenatal diagnosis [editorial]. N Engl J Med 1975;293:932-3. 2. Broome DL, Wilson MG, Weiss B, Kellogg B. Needle puncture of fetus: a complication of second-trimester amniocentesis. Am J Obstet Gynecol 1976;126:247-52. 3. Karp LE, Hayden PW. Fetal puncture during midtrimester amniocentesis. Obstet Gynecol 1977;49:115-7. 4. Rausko1b R, Fuhrmann-Rieger A, Fuhrmann W, Jovanovic V. Hautdefekte bei Neugeborenen oder Feten als fragliche Verletzungsfolge nach Amniozentese in der Friihschwangerschaft. Geburtshilfe Frauenheilkd 1978;38: 107-10.

Rummelt et al · Iris Cysts and Amniocentesis 5. Creasman WT, Lawrence RA, Thiede HA. Fetal complications of amniocentesis. JAMA 1968;204:949-57. 6. Fortin JG, Lemire J. Une complication oculaire de l'amniocentese. Can J Ophthalmol 1975;10:511-13. 7. Merin S, Beyth Y. Uniocular congenital blindness as a complication of midtrimester amniocentesis. Am J Ophthalmol 1980;89:299-30 1. 8. Isenberg SJ, Heckenlively JR. Traumatized eye with retinal damage from amniocentesis. J Pediatr Ophthalmol Strabismus 1985;22:65-7. 9. Admoni MM, BenEzra D. Ocular trauma following amniocentesis as the cause of leukocoria. J Pediatr Ophthalmol Strabismus 1988;25: 196-7. 10. BenEzra D, Sela M, Pe'er J. Bilateral anophthalmia and unilateral microphthalmia in two siblings. Ophthalmologica 1989; 198: 140-4. 11. Naylor G, Roper JP, Willshaw HE. Ophthalmic complications of amniocentesis. Eye 1990;4:845-9. 12. Cross HE, Maumenee AE. Ocular trauma during amniocentesis. Arch Ophthalmol 1973;90:303-4. 13. Grutzmacher RD, Lindquist TD, Chittum ME, eta!. Congenital iris cysts. Br J Ophthalmol 1987;71:227-34. 14. Naumann G, Green WR. Spontaneous nonpigmented iris cysts. Arch Ophthalmol 1967;78:496-500. 15. Naumann GOH, Rummelt V. Congenital nonpigmented epithelial iris cyst removed by block-excision. Graefes Arch Clin Exp Ophthalmol 1990;228:392-7. 16. Paridaens ADA, Deuble K, McCartney ACE. Spontaneous congenital non-pigmented epithelial cysts of the iris stroma. Br J Ophthalmol 1992;76:39-42. 17. Streiff JJ. Kryptenblatt und Kryptengrundblatt der Regenbogenhaut und die Entstehung der seri:isen Cysten an der vorderen Seite der Iris. Arch Augenh 1904;50:56-119. 18. Hogan MJ, Goodner EK. Surgical treatment of epithelial cysts of the anterior chamber. Arch Ophthalmol 1960;64: 286-91.

19. Maumenee AE, Shannon CR. Epithelial invasion ofthe anterior chamber. Am J Ophthalmol 1956;41:929-42. 20. Rum melt V, Naumann GOH. Block excision of congenital and infantile nonpigmented epithelial iris cysts: report on 8 infants. German J Ophthalmol 1992;1:361-6. 21. Naumann GOH, Rummelt V. Block excision of cystic and diffuse epithelial ingrowth of the anterior chamber. Report on 32 consecutive patients. Arch Ophthalmol 1992; 110: 223-7. 22. Naumann G, Vi:ilcker HE. Blockexzision intraokularer Prozesse. II. Epitheleinwachsung in das vordere Augensegment. Klin Monatsbl Augenheilkd 1975;166:448-57. 23. Klien BA, Tanner GS. Congenital epithelial cyst of the iris stroma. Am J Ophthalmol 1963;55:291-5. 24. Coburn A, Messmer EP, Boniuk M, Font RL. Spontaneous intrastromal iris cyst. A case report with immunohistochemical and ultrastructural observations. Ophthalmology 1985;92: 1691-5. 25. Koch K. Kongenitale Iriszyste. Klin Monatsbl Augenheilkd 1921;67:407-10. 26. Juselius E. Die spontanen Iriszysten, ihre Pathogenese und Entwicklung. Klin Monatsbl Augenheilkd 1908; 46(VI.band):300-10. 27. Politzer G. Die Entstehung der spontanen epithelialen Iriscysten. Graefes Arch Ophthal 1953;153:497-503. 28. Roy FH, Hanna C. Spontaneous congenital iris cyst. Am J Ophthalmol 1971;72:97-108. 29. Rush JA, Weinstein GW, Meriwether WA. Spontaneous nonpigmented iris cyst. Arch Ophthalmol 1982;100:304-5. 30. Laval J. Spontaneous cyst of the iris. Am J Ophthalmol 1947;30:55-7. 31. Witschel H, Berndt K, Mackensen G. Angeborene Stromazyste der Iris. Ein klinisch-histopathologischer Fallbericht. Klin Monatsbl Augenheilkd 1979; 174:572-6. 32. Shields JA. Primary cysts of the iris. Trans Am Ophthalmol Soc 1981 ;79:771-809.

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