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 clini- cally 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 sepa- rately. 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 pu- pillary 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 ten- dency 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 point- ed 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 ten- dency 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 in- volvement. 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 evi- dence 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 de- scribed 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 cham- ber 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 en- tirely 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.