Primary Cysts of the Iris

PRIMARY CYSTS OF THE IRIS

BY Jerry A. Shields, MD

INTRODUCTION PRIMARY IRIS CYSTS ARE RELATIVELY UNCOMMON, AND THERE HAVE BEEN NO LARGE studies which define the clinical characteristics and natural course of these lesions. The purpose of this thesis is to summarize the available literature on primary iris cysts, to review the clinical data on 62 affected patients who have been evaluated and followed by the author, and to document their clinical features with anterior segment photographs. On the basis of these observations, certain misconceptions in the literature regarding primary iris cysts will be challenged and a simple classification of such lesions will be proposed.

DEFINITIONS For purposes of this report a cyst is defined as an epithelial-lined space. A primary iris cyst is an epithelial-lined space which involves a portion of the iris and which has no recognizable etiology. A secondary iris cyst is an epithelial-lined space which involves a portion of the iris and which has a recognizable etiology, such as surgical trauma, nonsurgical trauma, or miotic drugs. Such secondary iris cysts have already been thoroughly and accurately described in the literature. They will be included in the overall classification but will not be included in the statistical part of this report.

REVIEW OF THE LITERATURE The literature on primary iris cysts is rather confusing because most reports have cited only a single example or a small series of patients and no writer has accumulated enough cases to classify the lesions into clinically meaningful categories. A review of the available literature indicated that such cysts may occur on the pupillary margin, in the posterior epithelial layer of the iris, or as free-floating cysts in the aqueous or vitreous chambers. Finally, in rare instances a cyst may appear to develop in the iris stroma. The literature on each type will be considered separately. TR. AM. OPHTH. SOC. vol. LXXIX, 1981 772 Shields~

CYSTS OF THE PUPILLARY MARGIN Very little has been written about primary cysts which occur at the pupillary margin and such lesions appear to be extremely rare. Fuchs' in 1931 described "congenital ectropion uveae," which appears in reality to have been cysts of the pupillary margin. Cowan2 in 1936 reported four patients, all of whom were members of one family. Each of his patients had bilateral, multiple, pigmented globular protuberances located at the pupillary margin of the iris. He pointed out the congenital, familial tendency of this condition, stressed the term "iris flocculi" to describe those cysts which had apparently ruptured spontaneously and emphasized the lack of ocular complications associated with such cysts. He supported the theory that they occurred secondary to a failure of closure of the annular sinus. Berliner,3 while not citing references, also stressed that iris flocculi formation is definitely hereditary, but not sex-linked. Duke Elder4 in 1974, reviewed the subject of iris flocculi, but he did not stress the cystic nature of this entity. The pathogenesis of these pupillary margin cysts is obscure. It seems feasible that they occur as a failure ofclosure ofthe anterior portion of the primitive optic cup (annular sinus ofvon Szily). Some authors have pointed out their similarity to the pigment processes normally hanging over the pupils of horses and cattle and suggested that they may represent atavistic vestiges.3 The pathology ofpupillary margin cysts has not been well-described in the literature. Berliner quotes Fuchs to have shown that they consist of "hyperplasia of the pigment epithelium with no enclosed connective tissue.,"3

CYSTS OF THE POSTERIOR IRIS EPITHELIUM Cysts which arise from the posterior epithelial layers of the iris have stimulated considerable interest in the literature because of their tendency to clinically resemble malignant melanomas of the ciliary body and iris. In many cases the patient has been mismanaged because the lesion could not be clinically differentiated from a melanoma. As early as 1897, Zimmerman5 reported a patient with bilateral involvement. Although the lesions were suspected to be malignant tumors, they were followed cautiously and showed no change over a follow-up period of four years. Bickerton6 in 1907 reported a case in which the cyst was suspected to be a malignant melanoma, but since it did not respond to treatment with potassium iodide and mercury, it was removed by iridectomy. Lowenstein and Foster7 in 1947 reported the histopathologic features of such a cyst which was found in an eye enucleated for a malig- Iris Cysts 773 nant melanoma of the limnbus, but they did not present convincing evidence for a relationiship betweeni the two lesionis. They provided a brief review of the literature and pointed out that only about 13 cases had been recorded as of 1940. Berliner8 in 1949 speculated that suchl cvsts were developmental ancd due to failure in fusion enibl)ryologically of the two posterior epithelial layers of the iris. Reese,9"'0 in a study of iris and ciliary body cysts which were discov- ered on histologic examination of eyes, pointed out that he had seen 12 cases clinically which belonged to this group. Vail and Merz" in 1951 described a rather large cyst of this type and reviewed the various theo- ries of pathogenesis. Scheie12 in 1953 added 16 cases to the literature and stressed the value of gonioscopy in the diagnosis of such lesions. The patient reported by Makley and King13 in 1958 had multiple cysts which so closely resembled a malignant melanoma that the eye was enucleated. The most thorough descriptions of the pathology of cysts of the iris epithelium have been provided by Reese,9"') Hogan and Zimmerman'4 and more recently by Meyer, Erlik and Foos.'5 The cysts are formed by a separation of the two layers of epithelium anywhere between the pupil and the ciliary body. The pathogenesis of these cysts is not entirely clear. Vail and Merz"l speculated that the condition results from a developmental event which takes place at about the 110 mm or four month stage. They suggest that traction of the zonules on the ciliary epithelium during growth of the eye allows for faulty apposition between the outer and inner layers of the optic cup in the irido-ciliary region. They point out that constant working of the zonules during accommodation may act as a mechanical irritant later in life and thus increase the size of the cyst. This may account for the fact that the condition is most often diagnosed clinically during adulthood. In support of this theory of pathogenesis, they quote Gartner,'16"7 who observed anomalous ciliary processes on the peripheral iris which could account for development of zonules with traction in the region of the irido-ciliary sulcus. Davidson,18 in a report of two cases, also supported this tractional theory.

FREE-FLOATING ANTERIOR CHAMBER CYSTS Pigmented cysts in the anterior chamber have been recognized for many years. Coats'9 in 1912 reported a case in which the cyst shifted with movement of the patient's head. Yanoff and Zimmerman2) in 1965 described a case in which the involved eye was enucleated because of suspected melanoma and reviewed the literature on the subject. Donald- son21 in 1967 presented clinical photographs of two cases. Fine22 reported 774 Shields a free-floating cyst in the anterior chamber which interfered with visioIl and required surgical removal. On the basis of a few cases studied histologically, these anterior chamber cysts appear to be lined by iris pigment epithelium and to contain clear fluid. In one reported case, the cyst was lined by 1)oth pigmented and non-pigmented epithelium.2"' The case reported bv Fine22 was entirely lined by deeply pigmented epithelium.

FREE-FLOATING VITREOUS CYSTS Perhaps because they are so fascinating clinically, a number of cases of free-floating vitreous cysts, presumably originating in the iris or ciliarv body, have been reported. Few authors, however, have recorded more than one such case. A typical case in a 17-year-old box was recorded by Tansley in 1899.23 A case of two cysts in the vitreous of one eve was recorded by Brewerton24 in 1912, but the clinical description was not clear. The cases reported by Shine in 1913,23 Scarlett in 1929,26 and bv Hurwitz in 1933,2' however, were typical cases. Additional isolated cases were reported by Meding28 and Seech29 in 1934, both of whom reviewed the literaure on the subject. Cassady3() in 1939 reported a typical case and provided another excellent review of the literature. He reported a second case in 1949.31 In recent years, case reports were added by Feman and Straatsma,32 Bullock,33 Elkington and Watson,34 Awan3' and Wolter, Martonyi and Smith.3" All of these cases had characteristic features of free-floating vitreous cysts to be described later. An interesting relationship between retinitis pigmentosa and vitreous cysts had been pointed out in several instances. Perera37 reported a case of bilateral vitreous cysts in a 55-year-old man with retinitis pigmentosa and cited other similar cases. It is not clear whether these cysts are related to the free-floating cysts which presumably take origin from the epithelium of the iris or ciliary body.

IRIS STROMAL CYSTS Primary cysts which develop in the iris stroma are extremely rare, with only a few cases reported in the English literature. This type of cyst characteristically occurs unilaterally in infants or young children. The case reported by Butler38 was on a 1-month-old child, that of Guerry and Wiesinger,39 was in a 3-year-old child, that of Klein and Tanner40 in a 4-month-old child, that of Roy and Hanna41 in a 2-month-old, and the case of Mullaney and Fitzpatrick42 in a 6-month-old. The two patients reported by Naumann and Green43 were in a 3-month-old and a 15- month-old child, respectively. Iris Cysts 775 In rare instances, cysts apparently of this type have occurred in adults. The case reported by Laval,44 which occurred in a 57-year-old man, may have been of this type. A similar case reported by Wilson45 in a 36-year- old man, was successfully treated by electrolysis. One of the four cases reported by Cleasby46 was apparently ofthis type. It occurred in a 7-year- old child but may have been present since birth. An analysis of the cases reported in the literature fails to detect any major clinical differences between those present at birth and those which appeared in adulthood.

CONCEPTS OF NATURAL COURSE AND COMPLICATIONS A number ofauthors have discussed the natural course and complications of primary cysts of the iris, particularly those which arise from the posterior epithelial layer. As recently as 1974, Duke-Elder47 made the following statement: "Although they may remain stable for a long time, the tendency is for them to grow slowly and steadily, ultimately bringing on secondary glaucoma and loss of vision." He continues, "as a rule, their evolution may be divided into 3 stages: (1) a symptom-free period, when no discomfort or visual disturbances arise; (2) an irritative period when an iridocyclitis may develop; (3) a period of raised tension which results in absolute glaucoma, vision being completely destroyed and excision of the eye usually being necessary because of pain." Finally, he stressed, "It is important, therefore, as soon as the diagnosis is made, to arrange for adequate treatment when the cyst is yet small, especially if it is seen to be growing in size, since the only ultimate result which can legitimately be expected, if events are allowed to take their course, is loss of the eye." Garron,48 in reporting a case in which the involved eye was enucleated because of suspected melanoma stated, "most cases are first observed after the onset of glaucoma. Usually the cysts have by then grown to a considerable size and the eye is removed because ofabsolute glaucoma or because malignant melanoma is suspected." The involved eye in his case had an intraocular pressure of 34 mm Hg. Chandler and Braconier49 reported three patients with multiple cysts who developed acute angle closure glaucoma.

OBJECTIVES OF CURRENT STUDY As the author evaluated additional patients with iris cysts, it gradually became apparent that many of the aforementioned statements from the literature, particularly with regard to the natural course and complications of these lesions, were not well-substantiated. These misconceptions 776 Shields were perhaps due to the tendency of physicians to report those cases which produced complications or which were managed by enucleation because of suspected melanoma. In addition, it was clear that no simple classification of the various types of iris cysts was available. The current study was, therefore, undertaken to study the clinical features, natural course and complications of iris cysts and to develop a classification of these lesions based upon the observations made.

PATIENTS, MATERIALS AND METHODS Detailed records were maintained on all patients with iris cvsts who were evaluated by the author between 1974 and 1980. One patient included in the study was not personally evaluated by the author but the clinical data and photographs were provided by a colleague. Each patient had a thorough history and comprehensive ocular examination, with emphasis upon slit lamp biomicroscopy, gonioscopy and special transillumination techniques to be described later. When possible, slit lamp photographs or goniophotographs were taken to document and follow the natural course of the cysts. When photographs were not possible because of the location of the lesions, drawings were made on the initial examination and on subsequent examinations. In addition to obtaining general data on patients with primary iris cysts, the author attempted to obtain information regarding referring diagnosis, associated systemic findings, medication history, associated ocular disorders, ocular complications, and natural course of the lesions. Follow-up data were obtained either by periodic examination of the patient or by communication with the referring ophthalmologists. Photomicrographs of the various types of cysts were obtained from pathologists who have had the opportunity to evaluate these lesions microscopically.

RESULTS During the course ofthe study, it became apparent that iris cysts could be divided into two main categories: primary and secondary types. The primary cysts did not have a recognizable etiology, but rather appeared to arise spontaneously. The secondary types were invariably associated with an obvious etiologic factor such as surgical trauma, non-surgical trauma or the prolonged use of topical miotic drugs. As mentioned earlier, the results described herein pertain only to primary iris cvsts. On the basis of clinical examination, primary cysts were divided into epithelial and stromal types. The cysts which arose from the posterior Iris Cysts 777 epithelial layer of the iris occurred either at the putpillarv miiargini, in the midzonal portion of the iris, in the peripheral portion of the iris at the base of the ciliarv body, or as a dislodged lesion in the anterior or vitreous chamibers. Each tvpe appeared to have a different clinical presentation and clinical significance. The cysts which arose within the iris stroma could not be categorized as to anatomic site, but could be divided inito congenital and acquired tvpes. Table I depicts the simple classificationl of these cysts which will be used to discuss them in the following para- graphs. Table II presents the general data on primarv iris cysts, which will be considered at this time.

CYSTS OF IRIS PIGMENT EPITHELIUM Cvsts which appeared to arise within the pigment epithelial layer of the iris were characteristically found in any of five locations: (1) the central or pupillary zone of the iris, (2) the midzone of the iris, (3) the peripheral or iridociliary zone of the iris, (4) in the anterior chamber or (5) in the vitreous chamber (Table I). The features of each type of cyst will be discussed separately.

TABLE I: PROPOSED CLASSIFICATION OF IRIS CYSTS I. PRIMARY CYSTS A. Cysts of iris pigment epithelium 1. Central (pupillarv) 2. Midzonial 3. Peripheral (iridociliary) 4. Dislodged a. Anterior chamber h. Vitreous chamber B. Cvsts of iris stroma 1. Congenital 2. Acquired II. SECONDARY CYSTS* A. Epithelial 1. Epithelial downgrowth cysts a. Post-surgical b. Post-traumatic 2. Pearl cysts 3. Drug induced cysts B. Parasitic *Secondary cysts are included in the classification but are not analyzed in this study.

1. CENTRAL (PUPILLARY) PIGMENT EPITHELIAL CYSTS Cysts which occurred at the pupillary margin were present in three patients (Table II). Because of their location, these were termed central 778 Shields

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H ) Q t--c 4.f1f~ '] 0-C]C Iris Cysts 779 cysts. One patient was an infant in whom the cysts were observed while the child was being evaluated for a retinoblastoma. They appeared as two dark brown lesions which were present at the 2:00 o'clock position in the eye containing the retinoblastoma (Fig 1). The cysts were so close togeth- er that they initially appeared as one cyst with a bilobed morphology. The retinoblastoma occupied the posterior segment of the eye and did not appear to be directly related to the cyst. Another patient was a 30-year- old man who had an isolated cyst measuring 1.5 mm in diameter located at the 10:00 o'clock position in the right eye. The second patient with central epithelial cysts was an 18-year-old man who gave a history of having the lesions since birth. The cysts were bilateral, multiple, and appeared as variable-sized, globular, dark brown structures which lined the pupillary border of the iris and projected into the pupillary aperture (Fig 2). Although some had ruptured and others

FIGURE 1 Anterior segment photograph showing two epithelial cysts at pupillary margin (central cysts) (arrow). 780 Shields

FIGURE 2 A: Close-up photograph of multiple epithelial cysts at pupillary margin in the right eye. B: Left eye. Note that one cyst in each eye has ruptured and its remnants cross the pupillary aperture. appeared confluent, about eight distinct cysts could be identified in each eye. The ruptured cysts were suspended as linear strands which crossed the pupil vertically and moved with movement of the iris. None of the lesions allowed appreciable transmission of light with transillumination techniques. The pupillary cysts in the infant and the 30-year-old showed no change over one year and three months follow-up periods respectively and the bilateral cysts in the teenager showed no change over a four-year follow- up period.

2. MIDZONAL PIGMENT EPITHELIAL CYSTS Five patients had epithelial cysts which were located predominantly in the midzone of the iris, between the pupillary margin and the iris root (Table II). These were classified as midzonal epithelial cysts. Two patients were men and three were women. Such cysts occurred bilaterally in three of the five patients and were multiple in all three bilateral cases, with an average of three cysts per eye. Two patients had a unilateral solitary cyst. All of the midzonal epithelial cysts had clinical features in common. In contrast to the central cysts, which were visualized without pupillary dilation, midzonal cysts were not easily visualized until the pupil was dilated. With early pupillary dilation, the cyst could be observed as a rounded dark brown mass just posterior to the pupillary border. With Iris Cysts 781

FIGURE 3 Close-up photograph through dilated pupil showing midzonal epithelial cyst in inferotemporal quadrant (arrow). Note the similarity to a ciliary body melanoma.

further dilation, the cyst gradually changed from a round to an elongated or fusiform shape, resembling a ciliary body melanoma (Fig 3). With maximal dilation, multiple round or fusiform cysts, not suspected on the initial examination, could often be visualized (Fig 4). These cysts characteristically had a thin wall which showed slight undulations with movement of the eye. Although they did not transmit light easily, occasional focal areas of pigment loss on the surface would allow minimal light transmission. These could be best visualized after the observer became dark-adapted. 782 Shields

FIGURE 4 Bilateral, multiple midzonal epithelial cysts. A: Right eye showing rounded cysts in temporal area (arrows). B: Left eye showing two fusiform cysts temporally (arrows).

One patient presented with severe nongranulomatous iritis in the left eye, which led to the diagnosis of a typical midperipheral cyst (Fig 5A). The cyst disappeared in one week while the patient was being treated with topical corticosteroids and cycloplegics (Fig 5B).

3. PERIPHERAL PIGMENT EPITHELIAL CYSTS Cysts located near the junction between the iris and ciliarv body (iridociliary sulcus) were by far the most common, accounting for 45 of the 62 patients in this series (Table II). These were classified as peripheral iris (iridociliary) cysts. They were decidedly more common in women, with 34 cases in females and 11 cases in males. The age of the patients ranged from 15 to 60 years. Most patients were in their twenties or thirties at the time of diagnosis. In contrast to central and mriidzonal cysts, peripheral epithelial cysts had a tendency to be unilateral and solitary. Of the 45 cases, 42 were unilateral and three were bilateral. Of the 48 total eyes involved, 46 had solitary cysts and two had multiple cysts. The two eyes with multiple cysts were in the same patient, who was noted to have bilateral multiple lesions during the second trimester of pregnancy. All peripheral cysts in this series were centered between either the 2:00 and 5:00 o'clock meridians or the 7:00 and 10:00 o'clock meridians, with an equal distribution between right and left eyes. No lesions of this type were found directly at the 12:00 o'clock or the 6:00 o'clock position. Iris Cysts 783

FIGURE 5 Inferior midzonal epithelial iris cyst in a 35-year-old man. The lesion was diagnosed during an attack of acute nongranulomatous iritis. One week later, after treatment of the iritis, the cyst had almost disappeared.

There was a marked tendency for the lesions to occur on the temporal side of the iris. Of the 46 eyes with solitary cysts, the lesion was located temporally in 39 cases (85%) and nasally in 7 cases (15%). Of those located on the temporal side, the cyst was located infero-temporally in 33 cases (85%). Thus, these lesions are by far more common between 7:00 and 9:00 o'clock in the right eye and between 3:00 and 5:00 o'clock in the left eye. In most cases, the peripheral cyst was recognized on routine slit lamp examination as a very subtle anterior displacement of the iris stroma at or just below the horizontal meridian (Fig 6A). The elevation could be best 784 Shields

FIGURE 6 A: Slit lamp characteristics of a peripheral epithelial iris cyst using diffuse illumination. A very subtle thinning of the iris stroma can barely be visualized (arrow). B: Slit beam view showing anterior bowing of the iris in the same area (arrow). appreciated by using a vertical slit beam (Fig 6B). In most instances, the overlying iris stroma was intact or only slightly thinned. Even with wide pupillary dilation, such cysts could not be directly visualized by routine

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FIGURE 7 View of peripheral epithelial iris cyst located in the iridociliary sulcus (arrows). The pupil is widely dilated. The lens is to the right of the arrows and the iris is to the left. Note the minimal compression of the .....l s p b t c iris Cysts 785 slit lamp techniques. By obtaining maximal pupillary dilation, rotating the slit lamp to the side, using a horizontal light beam, and tilting the bar of the slit lamp, however, the cyst wall was directly visualized between the iris and ciliary body in 33 of the 48 eyes involved (Fig 7). Using the Goldmann 3-mirror contact lens to further facilitate visualization of the peripheral portion of the posterior chamber, the cyst could be visualized in 45 of the 48 eyes. The most obvious abnormality on gonioscopy was a rounded anterior displacement of the peripheral portion of the iris stroma. With slight tilting of the lens, the thin-walled cyst could be visualized. In contrast to central and midzonal epithelial cysts, the peripheral cysts transmitted light readily, often allowing visualization of the ciliary processes through both walls of the lesion (Fig 8). In three cases, the cyst

FIGURE 8 Gonioscopic features of peripheral epithelial iris cyst located in the iridociliary sulcus. The black arrow depicts the typical anterior displacement of the iris stroma. The white arrow depicts the cyst behind the iris. Note that the cyst wall is clear, permitting visualization of the ciliary processes through the cyst. 786 Shields could not be directly visualized using this technique and the diagnosis remained presumptive. The typical anterior displacement of the iris stroma in the horizontal meridian in young adult women with no evidence of ciliary body tumor, however, provided strong support for the diagnosis. In the one patient with bilateral multiple peripheral epithelial cysts, the lesions were identical to the solitary cysts seen in most patients.

4. DISLODGED CYSTS-ANTERIOR CHAMBER In four of the 62 cases, a typical iris epithelial cyst was present in the anterior chamber, presumably having become dislodged and having passed from the posterior chamber through the pupil (Table II). Routine slit lamp biomicroscopy in these cases demonstrated a pigmented lesion in the peripheral iris, suggesting a pigmented tumor (Fig 9A). Gonios- copy, however, demonstrated the lesion to be lying on the surface of the iris, anterior to the iris stroma (Fig 9B). In three of the four cases the

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FIGURE 9 A: Epithelial cyst of iris which dislodged, migrated to the anterior chamber, and became fixed in the angle at 8:00 o'clock (arrow). B: Goniophotograph ofcyst shown in Fig 9A. Note that the lesion lies anterior to the iris stroma which is compressed posteriorly by the cyst. dislodged cyst had become fixed in the anterior chamber angle. One was fixed at the 8:00 o'clock position in the right eye and the other two were fixed in the angle at the 6:00 o'clock position. In one case, the anterior chamber cyst was not fixed, but was floating freely in the anterior chamber and moved with positioning of the patient's head (Fig 10). All cases of Iris Cysts 787

Fig A.C: Anterior segment view ithptientinsuineosis. t

FIGUTRE 10 A: Anterior segment view of free-floating cvst in anterior chamber with patient sitting, showing pigmented lesion in angle inferiorly. B: Gonioscopic view of same lesion shown in Fig IOA. c: Anterior segment view with patient in supine position. The cyst has migrated from the 6:00 o'clock to the 9:00 o'clock position. D: Anterior segment view with patient in supine position with neck extended. The cyst has migrated to the 11:00 o'clock position (arrow).

dislodged cysts in the anterior chamber were unilateral and solitary (Ta- ble II). The lesions characteristically did not transmit light, although small foci of depigmentation occasionally allowed slight transmission. In no case of dislodged cyst in the anterior chamber could the original site of the cyst be identified by routine slit lamp examination or gonioscopy. 788 Shields

5. DISLODGED CYSTS-VITREOUS CHAMBER Dislodged cysts were found in the vitreous chamber in one man and one woman patient (Table II). In both cases, the cyst was unilateral and solitary. In both instances the cyst was suspended in the gel of the mid-vitreous. It demonstrated only slight movement with movement of the eye and then returned promptly to its original position. These cysts had only minimal pigmentation on their walls and were transparent with both slit-lamp biomicroscopy and ophthalmoscopy, allowing visualization of the retinal architecture through both walls of the cyst (Fig 11).

FIGURE 11 Free-floating epithelial cyst in vitreous just inferonasal to optic disc. Note that the lesion is semitransparent, allowing faint visualization of the retinal vessels through its walls. iris Cysts 789 Although it is possible that a dislodged cyst could occur in the posterior chamber, no such cases were encountered in this series and none were found in the literature.

CYSTS OF THE IRIS STROMA Three patients had cysts which involved the iris tissue anterior to the pigment epithelium. They were classified as primary epithelial cysts of the iris stroma (Table II). One occurred in a two-year-old child in whom a clear cyst, presumably present since birth, was noted to be progressively enlarging over several weeks (Fig 12). The anterior wall of the cyst was

FIGURE 12 Congenital stromal cyst of iris in a two-year-old child. The lesion had doubled in size over a few weeks. Note the stretched blood vessels on the surface of the relatively clear cyst.

excised and the lesion did not recur. This was classified as.a congenital stromal cyst. Two stromal cysts developed in adults and were classified as acquired primary epithelial cysts of the iris stroma. One was located superiorly in a 790 Shields

FIGURE 13 Acquired stromal cyst of iris in a 24-year-old woman. The lesion is located superiorly and extends from the angle to the pupillary margin.

24-year-old woman (Fig 13). It had been first noted four years earlier and had supposedly shown very slow enlargement, but the patient remained asymptomatic and the cyst was essentially unchanged during-four years of follow-up by the author. There was no history of ocular trauma. The second acquired primary stromal cyst occurred in a 32-year-old man whose cyst was located temporally in the left eye (Fig 14A). The patient had a history of recurrent, mild ocular trauma from fistfights, but the globe had never been perforated. The cyst had appeared spontaneously and had shown progressive enlargement for three years. Because of recurrent ocular inflammation, the cyst was aspirated through the limbus using a 25 gauge needle. It became smaller and adhered to the corneal endothelium but did not recur during the two years of follow-up after aspiration (Fig 14B). In contrast to epithelial iris cysts, the stromal cysts were larger, had a clear anterior wall, a densely pigmented posterior wall, and contained clear fluid. Blood vessels could be seen on the anterior surface of the lesion (Fig 12). Iris Cysts 791

FIGURE 14 A: Acquired stromal cyst of iris in a 32-year-old man. The cyst is located temporally in the left eye and is encroaching upon the pupil. B: Appearance of the lesion shown in Fig 14A three months after aspiration of the cyst.

REFERRING DIAGNOSIS A referring diagnosis was received in 59 ofthe 62 cases ofprimary iris cyst (Table III). There were only three diagnostic possibilities which were entertained by the referring physician: (1) iris cyst, (2) cyst, rule out melanoma and (3) melanoma. One ofthe three central epithelial cysts was initially suspected to be a malignant melanoma. Three of the four midzonal epithelial cysts were initially diagnosed as melanoma and one was

TABLE III: PRIMARY CYSTS OF THE IRIS-REFERRING DIAGNOSIS NUMBER OF CASES WITH CYST, RULE NUMBER DIAGNOSIS OUT MELA- MELA- TYPE OF CASES SUBMITED CYST(S) NOMA NOMA Central 3 2 1 0 1 Midzonal 5 4 1 0 3 Peripheral 45 44 8 10 26 Dislodged, anterior chamber 4 4 2 1 1 Dislodged, vitreous 2 2 2 0 0 Stromal Congenital 1 1 1 0 0 Acquired 2 2 1 1 0 Total 62 59 16 12 31 792 Shields correctly recognized as an iris cyst. Of the 44 peripheral iridociliary cysts in which a referring diagnosis was received, only eight were initially diagnosed as an iris cyst. Ten patients were referred with the diagnosis of iris or ciliary body melanoma. In all, 36 of the 44 cases caused concern that the lesion could be a melanoma. Of the four pigment epithelial cysts which were present in the anterior chamber, two were correctly recognized as a cyst and two raised suspicion that the lesion could be a melanoma in the anterior chamber angle. The two cysts in the vitreous chamber were easily recognized as cysts and caused no diagnostic problem for the referring ophthalmologist. Of the three primary stromal cysts, two were correctly diagnosed as cystic lesions, but the other was referred specifically to exclude the possibility of melanoma.

ASSOCIATED SYSTEMIC FINDINGS The patients were carefully questioned as to any factors in the past medical history which could be related to the cysts (Table IV). Isolated cases ofhypothyroidism, hypertension, and sarcoidosis were revealed but no relationship to the iris cysts was detected. It is of interest that the only patient with multiple bilateral peripheral cysts was diagnosed as having the ocular lesions during the second trimester of her first pregnancy. Long term follow-up on this patient is not yet available.

RELATIONSHIP TO MEDICATIONS The patients were questioned as to any past or present medications (Table V). Four women ofchildbearing age had taken oral contraceptives prior to recognition of the cysts, five patients had taken various allergy medications, one was receiving indomethacin for arthritis, and one patient, with a unilateral peripheral epithelial cyst, had taken 0.5% pilocarpine in both eyes for six months because of borderline high intraocular pressures. The cyst did not appear to change in three years following cessation of the pilocarpine. In general, no relationship between the iris cysts and medications could be substantiated.

ASSOCIATED OCULAR FINDINGS An attempt was made to detect any current or prior ocular disorders which could possibly be related to the iris cysts (Table VI). One patient had viral conjunctivitis for three months before the cyst was diagnosed. Two patients with unilateral peripheral cysts gave a history of mild anteri- or uveitis in both eyes. Another had mild sarcoid iritis in the eye with the cyst. A 35-year-old man had severe nongranulomatous iritis at the time iris Cysts 793

TABLE IV: SYSTEMIC FINDINGS IN PATIENTS WITH PRIMARY CYSTS OF THE IRIS AGE SEX TYPE OF CYST SYSTEMIC DISEASE(S) 34 Female Peripheral Pneumonia-twice 43 Female Peripheral Meningitis, age 13 37 Female Peripheral Hypothyroidism 21 Female Peripheral Colitis; Hyper- tension 28 Female Peripheral Hypothyroidism; Sar- coidosis (only black patient in series) 47 Female Peripheral Laryngeal polyp; adult onset diabetes 25 Female Peripheral, OU First trimester of pregnancy 24 Female Stromal, acquired Hepatitis, age 21

that a midzonal cyst was diagnosed. The lesion disappeared in one week following treatment of the iritis (Fig 5). One patient had a Burgmeister's papilla and another had myelinated nerve fibers in the peripheral retina of the involved eye. Small anterior polar cataracts were present in both eyes of a 40-year-old man with bilateral midzonal epithelial cysts. A 28-year-old man with a dislodged cyst in the anterior chamber had recurrent toxoplasmic retinochoroiditis in the involved eye. Ofparticular interest was the presence of bullous retinoschisis occurring unilaterally in the same quadrant as a midzonal cyst in a 42-year-old woman. The three- month-old child with a central cyst had advanced retinoblastoma in the same eye. The eye was treated with irradiation and the cyst remained unchanged after six months offollow-up. A young man with a progressive stromal cyst gave a history of bilateral ocular trauma due to fistfights, but

TABLE V: MEDICATION HISTORY IN PATIENTS WITH PRIMARY CYSTS OF THE IRIS AGE SEX TYPE OF CYST MEDICATIONS 43 Female Peripheral Penicillin and sulfon- amides 19 Female Peripheral Oral contraceptives 30 Female Peripheral Oral contraceptives 45 Female Peripheral Indomethacin 42 Female Peripheral Oral contraceptives 19 Male Peripheral Pilocarpine 0.5% for 6 months (glaucoma suspect) 24 Female Stromal Oral contraceptives Five patients were taking various medications for allergies. 794 Shields

TABLE VI: OCULAR DISORDERS IN PATIENTS WITH PRIMARY CYSTS OF THE IRIS EYE(S) AGE SEX TYPE OF CYST WITH CYST OCULAR DISORDER(S) 34 Female Perinheral OD Viral conjunctivitis OD 3 months before 43 Female Peripheral OD Optic atrophy OS due to meningitis, age 13 27 Male Peripheral OS Corneal foreign body OS 2 weeks prior to diagnosis 31 Male Peripheral OS Recurrent iritis, OU 19 Male Peripheral OS Mild optic atrophy, OU unknown cause 28 Female Peripheral OS Mild sarcoid uiveitis, OS 48 Female Peripheral OS Iritis OU, 15 years prior to diagnosis 28 Female Peripheral OD Burgmeister's papilla, GD 34 Female Peripheral OD Peripheral myelinated nerve fibers, OU 42 Female Midzonal OD Bullous retinoschisis, OD-unilateral, same quadrant as iris cyst 35 Male Midzonal OS Non-granulomatous iritis (cvst disappeared in one week after treatment of iritis) 40 Male Nlidzonal OU Anterior polar cataracts, OU 3 mo. Male Central OS Retinoblastoma, OS 28 Male Dislodged, anterior OD Toxoplasmic retinocho- chamber roiditis, OD 32 Male Stromal OS Recurrent blunt trauma, OU with evelid ecchvmosis examination revealed no evidence of a prior perforation of the globe (Fig 14).

OCULAR COMPLICATIONS Of the 69 eyes with primary iris cysts (Table II), only two had slightly decreased visual acuity which could possibly be attributable to the cysts (Table VII). One peripheral epithelial cyst was present in an eye with 20/40 vision which was believed to be due to slight lenticular astigmatism. The patient with the stromal cyst and ocular trauma had a vision of 20/30 Iris Cysts 795

TABLE VII: OCULAR DISTURBANCES POSSIBLY ATIRIBUTABLE TO THE CYST(S) IN EYES WITH PRIMARY IRIS CYSTS (69 EYES: 62 PATIENTS) FINDING FREQUENCY COMMENTS Increased intraocular pressure 0/69 Corneal edema 0/69 Cataract 0/69 Lenticular astig- 1/69 Vision 6/12; minimal dis- matism tortion of zonules Iritis 1/69 Vision 6/9, large stromal cyst in eye with recurrent blunt trauma Total 2/69 Only 2 of 69 eyes had visual disturbance which was mild in both instances which was attributable to anterior segment inflammation. In the case of the man who had acute iritis and a midzonal epithelial cyst, the slightly decreased vision appeared to be due to the iritis and not due to the cyst. The other 66 involved eyes had normal visual acuity. No patient had increased intraocular pressure, corneal edema, or cataract in the involved eye.

NATURAL COURSE An attempt was made to determine the natural course ofthe primary cysts ofthe iris (Table VIII). In the three patients with central cysts, no change in the lesions was demonstrated during follow-up periods of 3, 12, and 48 months, respectively. Four of the patients with midzonal cysts also demonstrated no change in the cysts in either eye during an average follow-up of 35 months. As mentioned, the fifth patient demonstrated disappear- ance of a midzonal cyst when treated for acute iritis. Follow-up information was obtained on 39 of the 45 patients with peripheral cysts and six patients were lost to follow-up. Of the 38 patients with an average follow- up of 26 months, 31 cysts remained unchanged, seven were definitely smaller, and none became larger during the follow-up period. In four of the patients, the cyst gradually disappeared, with resolution of the anterior displacement ofthe iris and no further visualization of the lesion with gonioscopy. Two of the three stromal cysts demonstrated enlargement and were managed by surgical excision and aspiration respectively. 796 Shields

PATHOLOGY Representative examples of the histopathology of the types of iris cysts in the authors' classification are uncommon. No examples ofthe histopathology of the central (pupillary) type of iris pigment epithelial cyst were reviewed in this study, but examples are discussed in the older literature. 1'3 Previous reports on the pathology of iris cysts have not separated the midzonal from the peripheral cysts of the iris pigment epithelium. Since they are somewhat different with regard to clinical features, their histopathologic features were reviewed to determine whether these differences could be explained. The midzonal pigment epithelial cyst has been studied on a few occasions. The case of Mandelbaum cited by Reese9"0 and the case of Makley and King'3 depict good examples of the pathology of this type of cyst. A large cyst, extending from the root of the iris to the area of the sphincter muscle, is present on the posterior surface of the iris (Fig 15). The cyst is lined externally by the pigment epithelium, explaining its failure to transmit light in most instances. The extent and location of these cysts explain why they become visible when the pupil is widely dilated. This is enhanced by the proximity ofthe lesion to the iris collarette, which allows the cyst to be everted when the pupil is dilated. Cysts which arise from the peripheral portion of the iris (iridociliary sulcus) occur at a location where the nonpigmented epithelium of the ciliary body becomes continuous with the pigment epithelium of the iris (Fig 16). Therefore, in contrast to central and midzonal cysts, which are lined externally by iris pigment epithelium, the peripheral cysts transmit light because at least a part of their external surface is lined by nonpigmented epithelium. Their peripheral location is a considerable distance

TABLE VIII: FOLLOW-UP DATA ON PRIMARY CYSTS OF THE IRIS NUMBER AV LENGTH NUMBER WITH FOL- NUMBER NUMBER NUMBER OF FOLLOW- TYPE OF CYST OF CASES LOW-UP UNCHANGED SMALLER LARGER UP (MONTHS) Central 3 3 2 0 0 25 Midzonal 5 5 4 1 0 35 Peripheral 45 39 32 7 0 26 Dislodged-anterior chamber 4 4 4 0 0 30 Dislodged, vitreous chamber 2 2 2 0 0 28 Stromal 3 3 1 0* 2* 24 *Two stromal cysts showed progressive enlargement and became smaller after surgical excision and aspiration respectively. Iris Cysts 797

FIGURE 15 Histopathology of midzonal epithelial iris cyst. Note that the two lavers of the iris epithelium are separated and the posterior layer is thrown into folds (arrotw). Other cysts, not seen clinically are present in the pars plicata (hematoxylin and eosin, x 25).

FIGU'RE 16 Histopathology of peripheral epithelial iris cyst. Note the rounded clear lesion in the region of the iridociliary sulcus (hematoxylin and eosin, x 25). 798 Shields from the iris collarette, explaining their failure to evert when the pupil is dilated. No cases of free-floating anterior chamber cysts were obtained for histologic studv. The fact that some previouslv reported cysts of this type were lined completely by pigment epithelium,22 suggests that they originate as either central or midzonal cysts. Others which contain both pigmented and nonpigmented epithelium probably originate as peripheral cysts in the region of the iridociliary sulcus. No cases of free-floating vitreous cysts were reviewed histologically in this study. Their transmission of light and their minimal to moderate pigmentation suggest that they arise either from the iridociliarv sulcus or more posteriorly in the ciliary body. Although the histopathologic features are slightly different from case to case, most iris stromal cysts reported in the literature have been lined by stratified epithelium suggestive of surface epithelium. The presence of

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FIGURE 17 Histopathology of congenital epithelial cyst of the iris stroma showing stratified epithelium similar to that of conjunctiva (hematoxylin and eosin, x 85). Iris Cysts 799

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FIGURE 18 Periodic acid Schiff (PAS) preparation of another congenital epithelial cyst of iris stromia. showing conjunctival epitheliumn with goblet cells (dark staining cells) (PAS, x 250). goblet cells in several cases has suggested a similarity to conjunctival epithelium."-"4 The two cases obtained for histologic review in this study demonstrated the lesion to be lined by surface epithelium and to contain goblet cells (Figs 17 and 18).

DISCUSSION

CLASSIFICATION Based upon the clinical observations of these 62 cases and upon a review of the literature, a simple classification of primary cysts of the iris was devised (Table I). Cysts arising from the iris pigment epithelium were found to have different clinical characteristics, depending upon their anatomic location. Thus it was possible to use an anatomic classification for these lesions. Cysts arising within the iris stroma could not be classified anatomically, but could be separated into congenital and acquired forms. Hence, they are classified according to their time of onset. As the pathogenesis of each type of primary iris cyst becomes better understood, a more consistent classification may be developed. 800 Shields CLINICAL FEATURES The clinical observations on these 62 patients has provided enough data to make certain generalizations about the clinical features of the different types of primary iris cysts.

1. CENTRAL (PUPILLARY) CYSTS OF IRIS EPITHEUUM Central (pupillary) epithelial cysts of the iris are uncommon, accounting for three of the 62 cases in this series. These congenital cysts appear to occur in two forms. The first is a unilateral variety in which the cysts are single or multiple (Fig 1). These lesions are characteristically small, and are usually detected on routine biomicroscopy. They are not known to be familial. The second type of central cyst of the iris epithelium is bilateral and multifocal. According to the literature this variant can be familial.2'3 A number ofdeeply pigmented round to oval globular bodies are characteristically present on the pupillary margin (Fig 2). They can be seen on slit lamp examination without dilation of the pupil. Although these lesions can remain relatively stationary for many years, they sometimes enlarge slowly and even rupture, resulting in irregular fragments ofthick pigment epithelium at the pupillary margin (iris flocculi). Ifthe ruptured cyst is on the inferior margin of the pupil, it will appear as a ruffled irregular strand lying in front ofthe iris inferiorly, as occurred in one ofthe cases reported by Cowan.' When a cyst of the superior pupillary margin ruptures, it appears as a stalactite which vertically transverses the pupil (Fig 2). It is of interest that such pupillary strands are not often noticed by the patient, who generally remains asymptomatic. The lesions characteristically remain dark with transillumination, presumably due to their heavily pigmented walls.

2. MIDZONAL CYSTS OF THE IRIS EPITHELIUM Epithelial cysts which occur in the mid-portion of the iris are also relatively uncommon, accounting for only five of the 62 patients in this series (Table II). Although these midzonal epithelial cysts are occasionally described in the literature, they have not previously been given a separate classification from other iris cysts. The current study, however, suggests that they have different clinical features and deserve to be classified separately. Midzonal epithelial cysts of the iris are commonly bilateral and multiple. Routine examination through the undilated pupil generally fails to disclose any lesion attached to the pupillary border. With dilation of the pupil, one or more round cysts can be seen in the pupil. When the pupil iris Cysts 801 is fully dilated, the lesions become stretched and everted so that they appear as dark fusiform structures between the lens and the iris (Fig 4B). They characteristically fail to transmit light because of the dense pigment epithelial lining. The walls of these cysts may show a tremulous motion with movement of the eye.

3. PERIPHERAL CYSTS OF THE IRIS EPITHELIUM Cysts which occurred peripherally in the region of the iridociliary sulcus were by far the most common type in this series, accounting for 45 of the 62 cases (Table II). Although it is possible that some such cysts may have originated from the pars plicata of the ciliary body, they all appeared clinically in the region ofthe iridociliary sulcus and had consistent clinical features. The peripheral cyst characteristically presents as a unilateral anterior displacement ofthe iris stroma, most commonly the inferotemporal quadrant (Fig 6). The iris stroma anterior to the lesion is normal or slightly thinned. Although most cases in this series had only one cyst in one eye, a review of the literature suggests that multiple cysts commonly occur in the involved eyes. Most of these are located in the ciliary body, do not displace the iris, and are not of clinical significance. In contrast to central and midzonal epithelial cysts, the iridociliary cyst cannot be directly visualized on routine slit lamp examination, but can be seen by employing special techniques to be described shortly. In almost all cases the visual acuity and intraocular pressure is normal and the overlying cornea is clear.

DIFFERENTIAL DIAGNOSIS Because oftheir characteristic clinical features, central epithelial iris cysts are rarely confused with other conditions. The only lesions which appear similar clinically are the miotic-induced cysts which develop following prolonged topical use of phospholine iodide or other strong miotics.50 Miotic-induced cysts are acquired rather than congenital and the patient has a history of topical miotic therapy. Central epithelial iris cysts should never be clinically confused with malignant melanoma and no diagnostic difficulties occurred in the present series. The differential diagnosis of midzonal and peripheral epithelial iris cysts include iris melanoma, ciliary body melanoma, and other rare tumors of the iris and ciliary body such as leiomyoma, medulloepithelioma, and melanocytoma. These cysts can be differentiated from such iris tumors by routine slit lamp examination by virtue ofthe fact that the stroma over a cyst is normal or only slightly thinned. In contrast, the aforemen- 802 Shields tioned iris tumors actually arise from the iris stroma and do not displace it anteriorly. Thus, in the case of such tumors, a distinct mass involving the iris stroma can be directly visualized with routine slit lamp techniques. A melanoma or other tumor of the ciliary body can sometimes appear similar to a cyst in the iridociliary sulcus on routine examination. The use ofdiagnostic techniques as described in the next section should be helpful in making the differentiation. Certain tumors such as medulloepithelioma ofthe ciliary body can be quite cystic and can resemble primary cysts.5152 The age of the patient and the presence of a fleshy tumor of the ciliary body, however, should facilitate the diagnosis. The free-floating cyst in the anterior chamber should cause little diagnostic difficulty because of the movements of the lesion which occur with slight changes in the position of the patient's head. The fixed cyst, however, can be somewhat difficult to differentiate from a melanoma involving the anterior chamber angle. It differs from a melanoma by its smooth, rounded borders and by the fact that it does not blend into the iris stroma but rather displaces the iris stroma posteriorly. A nevus or melanoma in the angle is more sessile and is directly continuous with the iris stroma. There are very few entities wh?ch can be confused with a free-floating epithelial cyst in the vitreous. Other conditions which can produce vitreous cysts include parasitic infestations such as cysticercosis, retinitis pigmentosa, and persistent posterior hyaloid remnants. The cysts of cysticercosis are more motile and the head of the parasite can be recognized protruding from the cyst walls. The vitreous cysts associated with retinitis pigmentosa may be similar to those derived from the ciliary epithelium. 37 However, they are usually located near the optic disc and can be con- nected by strands to the disc or retina. Prepapillary hyaloid cysts are characteristically associated with a mass of fibrovascular tissue extending into the vitreous from the optic disc.53,54 The differential diagnosis of primary cysts of the iris stroma includes malignant melanoma and secondary iris cysts. Malignant melanomas are solid, rather than cystic on slit lamp examination and should be easy to differentiate from stromal cysts. Patients with secondary iris cysts usually have a history of surgical or non-surgical ocular trauma and frequently develop glaucoma, corneal edema and other complications.

DIAGNOSTIC TECHNIQUES Central epithelial cysts and midzonal epithelial cysts can be recognized by their typical appearance on slit lamp examination. Peripheral epithelial iris cysts, however, are more difficult to visualize and require certain Iris Cysts 803 diagnostic steps to exclude the possibility of malignant melanoma. In the course of evaluating the 45 patients with peripheral iris cysts in this series, the author has gradually developed the following essential steps in making this differentiation.

1. EXTERNAL OCULAR EXAMINATION In a patient in whom either a melanoma or a cyst is suspected, the diagnosis of cyst is supported by the absence of pigmentation or promi- nent episcleral vessels in the quadrant of involvement, findings which commonly occur with ciliary body melanomas.

2. PRE-DILATION BIOMICROSCOPY OF ANTERIOR SEGMENT The typical smooth anterior displacement of the iris suggests a cyst, particularly if it is located in the inferotemporal iris periphery in a young woman.

3. OBTAIN MAX!MAL PUPILLARY DILATION The pupil should be widely dilated with the physicians choice of mydriat- ic. Following maximal dilation with drops, a cotton pledget saturated with the same drugs can be placed in the inferior fornix for five minutes to obtain even more dilation. This extreme dilation is often essential if the lesion is to be directly visualized.

4. POST-DILATION BIOMICROSCOPY OF ANTERIOR SEGMENT Slit lamp examination should then be repeated with the pupil maximally dilated. The slit lamp arm and oculars are rotated to the side to permit direct visualization of the posterior chamber between the iris and the lens in the quadrant of the lesion. The slit beam is positioned horizontally and the bar is tilted slightly. By using this technique, the cyst can be directly visualized and retroilluminated in approximately 80% of cases. Some cysts have such thin, transparent walls that they can be overlooked by the inexperienced observer. One can usually distinguish the ciliary processes through the clear walls of the cyst. In contrast, a ciliary body melanoma would not permit visualization of normal ciliary processes in the quadrant of involvement.

5. GONIOSCOPY Gonioscopy is then performed for two reasons. First, it enables visualization of the trabecular meshwork. In the case of an iridociliary cyst, the trabecular meshwork is usually normal, although the anterior chamber 804 Shields angle can be narrowed in the quadrant of involvement. In the case of a melanoma, one can sometimes see the solid mass involving the iris root. Second, gonioscopy provides a better view of the cyst and allows better retroillumination. In eleven cases in this series, the cyst was not visualized until gonioscopy was performed.

6. SLIT LAMP TRANSILLUMINATION This technique is useful for the occasional cyst which does not retroilluminate well and in which melanoma is still a diagnostic consideration. Using the slit lamp technique described in step 3 or the gonioscopy technique described in step 4, the wall of the cyst is brought into clear focus. A fiber-optics transilluminator is then placed on the limbus in the quadrant ofthe lesion. The light of the slit lamp is then turned offand the cyst is transilluminated while the physician continues to observe it through the binoculars of the slit lamp. Using this technique, most cysts which fail to retroilluminate on routine slit lamp examination will show some degree of transillumination.

7. TRANSCLERAL TRANSILLUMINATION The detection of a cyst which transilluminates does not necessarily exclude the possibility of a melanoma. On a number of occasions a cyst of the iridociliary region has been found to represent the anterior manifesta- tion of a more posteriorly located melanoma. To exclude this possibility, the fiber-optic transilluminator is gently placed in the fornix 1800 from the lesion after instillation of topical anesthesia. The patient is then asked to look in the direction of the transillumination probe. This allows visualization of the shadows of the pars plicata and pars plana in the quadrant of the lesion. If the pars plana transmits light normally then it is unlikely that a ciliary body tumor exists posterior to the iridociliary cyst.

8. INDIRECT OPHTHALMOSCOPY Indirect ophthalmoscopy should be performed in all cases to further exclude the possibility of a tumor in the peripheral choroid or to detect other fundus pathology. No special diagnostic techniques are helpful for stromal cysts ofthe iris. Slit lamp examination and gonioscopy will establish the diagnosis and the extent of the lesion.

ASSOCIATION WITH SYSTEMIC DISEASES Although patients with primary iris cysts were found to have occasional iris Cysts 805 systemic diseases, no specific diseases could be associated with their occurrence in this series (Table IV). It is known that there is a higher incidence of pars plana cysts in patients with multiple myeloma and other dysproteinemic states.55 Although the patients in this series did not have a complete laboratory investigation to exclude multiple myeloma and related diseases, none had signs or symptoms related to these conditions. On the basis of this study, it appears that primary cysts of the iris are unrelated to any particular systemic disease.

RELATION TO MEDICATIONS The use ofcertain medications has been associated with the development of iris cysts, particularly the miotic drugs used to treat glaucoma and accommodative strabismus, which predispose to the development of pupillary margin cysts.50 Oral contraceptives were the only medications which were used frequently by the patients in this series (Table V). This is not surprising, since many women of childbearing age, in whom such cysts are most often found, are taking oral contraceptives. In addition, one-third of involved patients were males who were taking no medications. It is concluded that no apparent relationsip exists between local or systemic medications and the development of primary iris cysts.

ASSOCIATED OCULAR DISORDERS There were a surprisingly large number ofocular disorders in the patients in this series with primary cysts of the iris (Table VI). Most of them, however, appeared to be coincidental. It is pertinent that several patients had ocular inflammatory disease, particularly iritis. For the most part, however, the inflammation was either mild or inactive. In one remark- able case, however, a large midzonal cyst was noted when a patient presented with severe iritis of undetermined cause. The cyst became much smaller and almost disappeared with resolution of the iritis. This suggests that ocular inflammation, in selected cases, may either con- tribute to the development of cysts or may cause pre-existing cysts to become larger. It must be stressed, however, that most cysts were not associated with past or present inflammation.

OCULAR DISTURBANCES ATTRIBUTABLE TO CYSTS In this study only two of the 69 involved eyes had mild visual distortion which could possibly be attributable to the cyst (Table VII). It is notewor- thy that none of the 69 eyes had elevated intraocular pressure. In view of the statements of Duke-Elder,47 Garron,48 and Chandler and Bracon- ier,49 who stressed the high frequency of glaucoma and other complica- 806 Shields tions, it is surprising to find such a low incidence of ocular complications in this series. This discrepancy must be due to the fact that only the large cysts which produce complications are usuallv reported. Since Duke- Elder extracted his data from the available literature, it is not surprising that he would find a high incidence of complicatioins. The patienits of Chandler and Braconier49 were referred to the authors because of their special interest in glaucoma, so it is not surprising that three of their four patients had elevated intraocular pressure in the involved eve. Based upon the results of this study, it must be concluded that, con- trarv to reports in the literature, the complication of glaucoma must be extremely rare. Indeed, visual disturbances of any sort directlv attributable to the cysts are extremely unusual. The natural course of primarv cysts of the iris depends largely upon the type of cyst (Table VIII). Those cysts which arise from the posterior pigment epithelium of the iris are remarkably stable, rarelv grow after the diagnosis is made, and frequentlv become smaller or even disappear clinically. This may be related to the fact that the posterior pigment epithelium of the iris has little secretorv tendencv, explaining the failure of most such cysts to become distended and to clinicallv enlarge. Cysts which arise from the iris stroma, on the other hand, often show a tendenev to progressively enlarge. This may be related to the fact that they are lined by surface epithelium, which often contains goblet cells.40'43 Such an epithelium has a greater secretory tendency and these cvsts are more likely to gradually distend and become progressively larger. It is concluded that the great majority of primary iris cysts are stable, nonprogressive lesions which rarely produce complications.

SUMMARY This paper has presented the author's experience with the evaluation and follow-up of 62 patients with primary cvsts of the iris. On the basis of these observations, a classification of iris cyst is proposed. Accordingly, primary iris cysts are divided into epithelial and stromal categories, each having different clinical characteristics. Epithelial cysts arise between the pigmented epithelial layers of the iris and occur at the pupillary margin (central cysts), in the mid-portion of the iris (midzonal cysts) or, more commonly, in the iridociliary sulcus (peripheral cysts). In some cases, the cysts apparently break free from their epithelial attachment and migrate into the anterior chamber or vitreous chamber (dislodged cysts). Primary stromal cysts occur within the iris stroma and are not directly continuous with the posterior epithelium. They apparently arise from ectopic surface Iris Cysts 807 epithelium which is trapped in the iris during embryologic development. A study of the natural course and complications of these lesions has shown that the great majority of primary iris cysts, particularly those which arise from the iris pigment epithelial layer, are stationary lesions which rarely progress or cause visual complications. This finding is con- tradictory to the contemporary beliefofcertain authorities who stress that many such lesions lead to severe complications with blindness and loss of the eye. The natural course of primary epithelial cysts differs from that of secondary iris cysts which follow surgical or non-surgical trauma. The latter lesions do frequently enlarge and lead to severe complications such as inflammation and glaucoma. The major clinical importance of primary iris cysts lies in their similarity to neoplasms of the iris and ciliary body. Clinical features helpful in making this differentiation are presented. Ancillary steps, particularly certain transillumination techniques, which are helpful in the diagnosis are discussed. It is concluded that the great majority ofprimary iris cysts are ophthalmic curiosities which require no treatment.

ACKNOWLEDGMENTS Figure 12 was provided by Dr P. Robb McDonald, Figure 15 by Dr Torrance Makley, Figure 16 by Dr Robert Foos, and Figures 17 and 18 by Dr W. Richard Green.

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