Iridocorneal Endothelial Syndrome Masquerading As Iris Melanoma in 71 Cases

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ONLINE FIRST Iridocorneal Endothelial Syndrome Masquerading as Iris Melanoma in 71 Cases

Carol L. Shields, MD; Margaret V. Shields; Vanessa Viloria; Haley Pearlstein; Emil Anthony T. Say, MD; Jerry A. Shields, MD

Objective: To describe the clinical features of iridocor- monly found with iris melanoma. The mean extent of iris neal endothelial (ICE) syndrome in a group of patients atrophy was 2 clock hours. Ectropion iridis was unidi- referred because of suspected iris melanoma. rectional in 10 and multidirectional in 14. Additional features of ICE included corneal endothelial guttata-like Methods: In a noncomparative case series, we per- changes in 33 (46%), corneal edema in 7 (10%), iris pig- formed medical record review for clinical features of ICE ment epithelial transillumination defects in 12 (17%), syndrome in 71 patients. polycoria in 1 (1%), and secondary glaucoma with intraocular pressure higher than 22 mm Hg in 7 (10%). Results: At presentation, the median patient age was 54 years. All patients were referred for evaluation of a pig- Conclusions: Iridocorneal endothelial syndrome can mented iris mass, suspected to be a melanoma. The iris simulate iris melanoma. Features more suggestive of ICE color was blue or green in 51 (72%) and brown in 20 syndrome include corneal endothelial guttata-like changes (28%). The mass proved to be a combination of iris stro- and edema, peripheral anterior synechia, multidirec- mal atrophy in 41 cases (58%) with exposure or loss of tional ectropion iridis, and iris atrophy. the underlying iris pigment epithelium; ectropion iridis in 24 (34%), imparting a disfigured iris with dark- brown color; iris nodules in 5 (7%); traction elevation Arch Ophthalmol. 2011;129(8):1023-1029. with iris distortion from peripheral anterior synechia in Published online April 11, 2011. 57 (80%); and corectopia in 53 (75%), a feature com- doi:10.1001/archophthalmol.2011.70

RIDOCORNEAL ENDOTHELIAL (ICE) was noted in 8 (22%). They commented syndrome is a spectrum of that eyes with Chandler syndrome mani- diseases that display common fea- fested more severe corneal edema whereas tures of corneal endothelial those with essential iris atrophy and Co- abnormality leading to broad- gan-Reese syndrome showed more ad- basedI peripheral anterior synechiae, iris vanced secondary glaucoma. stromal nodules, and traction-related iris The diagnosis of ICE syndrome is based Author Affiliations: Ocular stromal atrophy and iris hole forma- on the presence of clinical abnormalities Oncology Service, Wills Eye tion.1-4 The end result of this condition is involving the corneal endothelium, ante- Institute, Thomas Jefferson secondary angle-closure glaucoma.1-8 This rior chamber angle, and iris, often con- University (Drs C. L. Shields, Say, and J. A. Shields and condition is often divided into essential firmed with imaging modalities of specu- Mss Shields, Viloria, and (progressive) iris atrophy, Chandler syn- lar microscopy, confocal microscopy, Pearlstein), and College of Arts drome, and Cogan-Reese syndrome. Cor- ultrasound biomicroscopy, and anterior seg- and Sciences, University of neal edema and glaucoma are the leading ment optical coherence tomography.9-12 Oc- Pennsylvania (Ms Pearlstein), causes of visual loss in this syndrome. In casionally, the features are subtle and this Philadelphia, and Biology a series of 37 patients with ICE syn- condition is overlooked. Laganowski and Department, Franklin and drome, Wilson and Shields5 classified 8 coworkers6 evaluated 33 patients with ICE Marshall College, Lancaster (Ms Shields), Pennsylvania; and (22%) with essential iris atrophy, 21 (57%) syndrome–related secondary glaucoma and College of Science, University with Chandler syndrome, and 8 (22%) noted that the underlying diagnosis of ICE of Notre Dame, Notre Dame, with Cogan-Reese syndrome. End-stage syndrome was initially overlooked in 17 Indiana (Ms Viloria). glaucomatous cupping of the optic disc (68%).

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1. Iridocorneal Endothelial Syndrome Simulating Table 2. Iridocorneal Endothelial Syndrome Simulating Iris Melanoma in 71 Eyes Iris Melanoma in 71 Eyes

No. (%) No. (%) Demographic Features (N=71 Eyes) Clinical Features (N=71 Eyes) Age, y, mean, median (range) 51, 54 (18-80) Visual acuity Sex Ͼ20/50 62 (87) M 17 (24) 20/50-20/100 7 (10) F 54 (76) Ͻ20/100 2 (3) Race IOP,mmHg White 67 (94) Յ22 64 (90) African American 3 (4) 23-35 5 (7) Asian 1 (1) Ͼ35 2 (3) Hispanic 0 Corneal/scleral features Ocular history Corneal guttata 33 (46) Glaucoma 11 (15) Corneal edema 7 (10) Herpes keratitis, simplex and zoster 5 (7) Corneal opacity/scar 5 (7) Previous eye surgery (including laser) 10 (14) Episcleral vessels dilated 6 (8) Others 10 (14) Iris features Duration of symptoms, mo, mean, median (range) 24, 4 (0-240) Corectopia 53 (75) Main referral diagnosis Ectropion iridis 24 (34) Iris melanoma 62 (87) Iridocorneal touch 20 (28) Iris cyst r/o melanoma 2 (3) Iris nodule 5 (7) Iridocorneal endothelial syndrome r/o melanoma 7 (10) Transillumination defect 12 (17) Duration of follow-up before referral, mo, mean, 16, 3 (0-120) Iris atrophy 41 (58) median (range) Polycoria 1 (1) Presenting symptom No. of sites of ectropion uvea per iris, mean, 4.2, 3.0 (1-12) Asymptomatic 19 (27) median (range) Decreased vision 8 (11) Iridocorneal touch, clock hours, mean, 3.9, 3.0 (1-10) Eye redness 2 (3) median (range) Eye pain 4 (6) Extent iris atrophy, clock hours, mean, 4.2, 4.0 (1-10) Abnormal pupil 33 (46) median (range) Heterochromia 3 (4) PAS Involved eye Mean clock hours, median (range) 4.9, 4.0 (1-12) Right eye 37 (52) Anterior to the Schwalbe line 44 (62) Left eye 34 (48) Broad PAS 46 (65) No PAS 14 (20) Abbreviation: r/o, rule out. Optic nerve head Cup-disc ratio Ͼ0.5 7 (10) Optic disc-cup asymmetry 2 (3) Because of the broad phenotype of ICE syndrome, the differential diagnosis encompasses many conditions in- Abbreviations: IOP, intraocular pressure; PAS, peripheral anterior cluding Fuchs endothelial dystrophy, posterior polymor- synechiae. phous dystrophy, iris stromal hypoplasia, Rieger syndrome, aniridia, iridoschisis, ectopia lentis et pupillae, segment features including heterochromia; sentinel vessels; cor- inflammatory nodules, Lisch nodules, iris flocculi (pig- 2 neal edema, scarring, or endothelial changes; corectopia; poly- ment epithelial cysts), and iris melanoma. The ICE syn- coria; ectropion iridis; iris nodularity, atrophy, or synechia; and drome features of corectopia, ectropion iridis, dark iris mass iris pigment epithelial defects. from iris stromal atrophy uncovering darker pigment epithelium, iris nodules from endothelial growth on the iris RESULTS stroma, and synechia-related distortion of the iris could lead to the mistaken diagnosis of iris melanoma. In this report, we describe 71 patients referred with the presumed diag- There were 71 eyes of 71 patients referred for evalua- nosis of iris melanoma who ultimately proved to have ICE tion of iris melanoma and found to have ICE syndrome. syndrome. The patient demographics are listed in Table 1. The mean age was 51 years and 54 (76%) were female and 17 (24%), male. Known glaucoma was present in 11 (15%) and her- METHODS pes keratitis in 5 (7%). A history of ocular trauma was disclosed in 7 and family history of glaucoma in 3 (4%), The computer-coded records of all patients evaluated on the corneal disease in 2 (3%), and cutaneous melanoma in Ocular Oncology Service at Wills Eye Institute were reviewed 2 (3%). Symptoms included abnormal pupil in 33 (46%), for codes for iris pseudomelanoma and iridocorneal endothe- decreased vision in 8 (11%), eye pain in 4 (6%), hetero- lial syndrome between July 1974 and August 2010. Each record was evaluated for patient age at detection of ocular abnor- chromia in 3 (4%), and eye redness in 2 (3%), and symp- mality, race, sex, medical conditions, ocular conditions, ocular toms were absent in 19 (27%). trauma, and family history of eye disease. The referral diagno- The ocular features are listed in Table 2. The iris color sis was listed. Each eye was evaluated for symptoms, lateral- was blue or green in 51 (72%) and brown in 20 (28%). ity, visual acuity, intraocular pressure, iris color, and anterior Intraocular pressure was higher than 22 mm Hg in 7 (10%)

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C D

Figure 1. Iridocorneal endothelial syndrome with peripheral anterior synechia and corectopia masquerading as iris melanoma because of iris contraction imparting a darker color at the 4:30 meridian (A), visible darker-colored iris adherence to the cornea in the angle region at the 2:00 meridian (B), iris stromal atrophy exposing a darker iris pigment epithelium at the 2:30 meridian (C), and extensive corectopia with a yellow-white angle mass from iridocorneal adhesion at the 4:30 meridian (D).

A B

C D

Figure 3. Iridocorneal endothelial syndrome simulating iris melanoma in a middle-aged woman with a unilateral brown iris mass (A) that represented iris pigment epithelial adhesion to the corneal endothelium (B and C).

Figure 2. Iridocorneal endothelial syndrome simulating iris melanoma with features of dark ectropion iridis (A and B), iridocorneal adhesion from the volvement of the trabecular meshwork with membrane 1:00 to 5:00 and 6:00 to 10:00 meridians (C), and extensive iris atrophy overgrowth leads to angle-closure glaucoma.2 Studies have exposing the underlying iris pigment epithelium (D). Note the subtle multidirectional ectropion/corectopia toward the 12:00, 3:00, and 8:30 demonstrated that “ICE cells” are pleomorphic and large, meridians (B) and more obvious multidirectional traction toward the 1:30 with features of epithelial cells, including desmosomes, and 8:00 meridians (D). tonofilaments, and microvilli.3,13,14 The ICE cells show a similar profile of differentiation as normal limbal epithelial cells.13 This acquired endotheliopathy is speculated and higher than 35 mm Hg in 2 (3%). The most com- to arise from herpes simplex viral origin.15 mon corneal features were endothelial guttata-like changes Most previously reported clinical series of patients with in 33 (46%) and edema in 7 (10%). The most common ICE syndrome have emanated from glaucoma depart- iris features were corectopia in 53 (75%), iris stromal at- ments.1,2,5-7 In 1978, Shields and coauthors1 reported 82 rophy in 41 (58%), and ectropion iridis in 24 (34%), with patients in their series of “the essential iris atrophies” and ectropion extending in a median of 3 separate direc- noted 56 (68%) were female and 63 (77%) had glau- tions per iris (Figures 1, 2, and 3). Peripheral ante- coma (Table 3). Ocular features included corectopia in rior synechia were present in 57 (80%) and were broad Ն 58 (71%), ectropion iridis in 23 (28%), and polycoria in based ( 2 clock hours) in 46 (65%). 20 (24%). In 1989, Wilson and Shields5 described the clinical features in 37 patients with ICE syndrome show- COMMENT ing features of corneal edema in 14 (38%), peripheral anterior synechia in 34 (92%), corectopia in 27 (73%), ec- The underlying abnormality in ICE syndrome is the pro- tropion iridis in 10 (27%), iris nodules in 7 (19%), and liferation of corneal endothelial cells and Descemet mem- iris stromal atrophy in 20 (54%). In that series, the main brane over the trabecular meshwork and onto the focus was secondary glaucoma and the intraocular pres- iris.3,4,13,14 Progressive enlargement and contraction of this sure was elevated over 22 mm Hg in 21 eyes (57%) and membrane leads to iris traction with corectopia and ec- over 35 mm Hg in 6 (16%), with 8 eyes (22%) display- tropion iridis and eventual traction-related iris stromal ing an advanced cup-disc ratio of 0.9 to 1.0. In 1992, La- atrophy and iris pigment epithelial holes. Further in- ganowski and coauthors6 identified 66 patients with ICE

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 3. Comparison of Iridocorneal Endothelial Syndrome From Glaucoma Department vs Ocular Oncology Department

No. (%)

Glaucoma Department Ocular Oncology Shields et al,1 Wilson and Laganowski et Teekhasaenee Department: 1978 Shields,5 1989 al,6 1992 and Ritch,7 2000 Current Series (N=82 Eyes) (N=37 Eyes) (N=66 Eyes) (N=60 Eyes) (N=71 Eyes) Age at presentation, y, mean 39 42 45 44 51 Sex F 56 (68) 23 (62) 35 40 (67) 54 (76) M 26 (32) 14 (38) 31 20 (33) 17 (24) Classification Cogan-Reese NAa 8 (22) 3 (45) 38 (63) 12 (17) Chandler syndrome 55 (67) 21 (57) 24 (36) 14 (23) 24 (34) Essential iris atrophy 27 (33) 8 (22) 39 (59) 8 (13) 35 (49) Features Corneal edema 41 (50) 14 (38) 18 (72) 25 (42) 7 (10) Iris corectopia 58 (71) 27 (73) NA 59 (98) 53 (75) Iris ectropion 23 (28) 10 (27) NA 42 (70) 24 (34) Iris polycoria 20 (24) 8 (22) NA 13 (22) 1 (1) Glaucoma 63 (77) 16b(43) 33 (50) 46 (77) 11 (15)

Abbreviation: NA, not addressed. a In this series, the classification was made for only Chandler syndrome or essential iris atrophy; however, 9 eyes in this series had iris nodules and might have represented Cogan-Reese syndrome. b The incidence of glaucoma was not specifically stated but 16 eyes had a cup-disc ratio of 0.7 to 1.0.

Table 4. Clinical Features of Iridocorneal Endothelial Syndrome vs Iris Melanoma

No. (%)

Iridocorneal Endothelial Syndrome Simulating Iris Melanoma: Iris Melanoma: Current Series Shields et al,16 2001 (N=71 Eyes) (N=169 Eyes) Age at presentation, y, mean 51 48 Sex F 54 (76) 84 (50) M 17 (24) 85 (50) Cornea/sclera features Corneal guttata 33 (46) 0 Corneal edema 7 (10) 0 Scleral sentinel vessels 6 (8) 43 (25) Extrascleral extension of tumor 0 10 (6) Iris features Iris mass/nodule 5 (7) 121 (72) Iris tumor seeds 0 94 (56) Iris atrophy 41 (58) 0 Corectopia 53 (75) 104 (62) Ectropion iridis 24 (34) 75 (44) Single meridian 10 75 Multiple meridians 14 0 Polycoria 1 (1) 0 Anterior chamber angle features Solid mass in angle 0 77 (46) Angle seeding 0 96 (57) Peripheral anterior synechiae 57 (80) NA Intraocular pressure Ͼ22 mm Hg 6 (8) 50 (30) Ͼ30 mm Hg 3 (4) 29 (17) Mechanism of glaucoma Angle closure 10 (100) 0 Angle obstruction by tumor 0 50 (100)

Abbreviation: NA, not addressed as this is not a typical feature of iris melanoma and should be distinguished from angle invasion of melanoma.

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Iris Melanoma

Iridocorneal Circumscribed Trabecular Meshwork Clinical Features Endothelial Syndrome Melanoma Diffuse Melanoma Melanoma Cornea/sclera features Corneal guttata ϩϩϩ −− − Corneal edema ϩϩ ϩ ϩ ϩ Scleral sentinel vessels − ϩϩ ϩ ϩ Extrascleral extension of tumor − ϩϩ ϩ Iris features Iris mass − ϩϩ ϩϩ − Iris atrophy ϩϩ −− − Corectopia ϩϩϩ ϩϩ ϩϩ − Unidirectional ϩϩϩ − Multidirectional ϩϩ − ϩ − Ectropion iridis ϩϩ ϩϩ ϩϩ − Heterochromia ϩ ϩ ϩϩϩ − Polycoria ϩ −− − Anterior chamber angle features Angle seeding − ϩ ϩϩ ϩϩϩ Peripheral anterior synechiae ϩϩϩ −− − Elevated intraocular pressure ϩϩϩ ϩ ϩϩ ϩϩϩ Mechanism of glaucoma ϩϩ −− − Angle closure − ϩϩ ϩϩ Angle obstruction by tumor Ciliary body features Shadow on transillumination − ϩϩ ϩ Optic disc features Optic disc cupping ϩϩ − ϩϩϩ

Abbreviations: ϩ, present; −, absent. The degree of presence is indicated by multiple ϩ’s.

syndrome and found 33 (50%) with glaucoma, com- coma (Tables 2 and 4). Iris melanoma classically mani- menting that the underlying diagnosis of ICE was over- fests as a circumscribed or diffuse tumor16-19 (Table 5) looked in 25 of the 33 with glaucoma. They emphasized (Figure 4). In a report on 169 eyes with iris mela- that the diagnosis of ICE syndrome should be consid- noma, the tumor was classified as circumscribed in 121 ered in younger patients with unilateral glaucoma. More (72%) and diffuse in 47 (28%).16 The circumscribed recently, Teekhasaenee and Ritch7 described ICE syn- tumor appears as a solitary, nodular, pigmented mass drome in 60 Thai patients and noted similarities of fe- within the iris stroma, often with intrinsic vessels and male preponderance and middle-age onset compared with feeding vessels and surrounding tumor seeding on the white series. They could visualize a translucent mem- iris stroma or within the angle (Figure 4). The diffuse brane (representing endothelial overgrowth) in these form appears as a minimally thickened, irregular sheet Asian eyes, as the membrane contrasted against the dark of pigmented cells on the iris surface, often with sec- brown irides. ondary glaucoma from angle invasion (Figure 4).16,17,19 Our cohort is different from previous series as our cases There is an unusual variant of diffuse melanoma in emanate from an ocular oncology department and all pa- which the malignancy arises solely in the trabecular tients were referred with the presumed diagnosis of iris meshwork, producing secondary glaucoma without an melanoma. In comparison with those from glaucoma de- obvious mass.20 partments1,5-7 (Table 3), our cases are similar in that there A comparison of the clinical features of ICE syn- was a female preponderance and the condition occurred drome in this series with iris melanoma16 shows simi- in middle-aged white individuals. However, our cases dif- larities and differences (Table 4) (Figures 1, 2, 3, and 4). fer in that there was far less glaucoma (15% vs 43%- The similarities (ICE syndrome vs melanoma) include 77%), less corneal edema (10% vs 38%-72%), and less poly- mean age at presentation (51 years vs 48 years), promi- coria (1% vs 22%-24%). Additionally, the eyes in our series nent episcleral blood vessels (8% vs 25%), corectopia (75% were more often subclassified with essential iris atrophy vs 62%), ectropion iridis (34% vs 44%), and elevated in- (49% vs 13%-33%) than most glaucoma series,1,5,7 except traocular pressure (8% vs 30%). Iridocorneal endothe- that of Laganowski and coworkers6 (59%). lial syndrome–related glaucoma is caused by membrane In our series, the referring diagnosis of iris mela- overgrowth onto the trabecular meshwork often lead- noma was suspected from features of iris nodules, iris ing to an angle-closure mechanism,6 whereas melanoma- elevation and distortion (corectopia, ectropion iridis) related glaucoma is usually from trabecular meshwork from peripheral anterior synechia, iris atrophy with infiltration by tumor.21,22 The differences include fea- exposure of underlying iris pigment epithelium, and the tures found primarily with ICE syndrome such as cor- combined features with the presence of secondary glau- neal guttata-like changes (46% vs 0%), corneal edema

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D E F

Figure 4. Spectrum of iris melanoma with corectopia. Pigmented iris melanoma with corectopia (A-F), subtle ectropion iridis (B, D, and E), and prominent episcleral vessels (A, B, and D-F). The melanomas were classified as circumscribed (A-C, E, and F) and diffuse (E). Note the subtle adjacent iris seeding (A) and extensive seeding (D and E).

(10% vs 0%), peripheral anterior synechiae (80% vs 0%), Published Online: April 11, 2011. doi:10.1001 iris atrophy (58% vs 0%), iris transillumination light trans- /archophthalmol.2011.70 mission (17% vs 0%), and multidirectional ectropion Correspondence: Carol L. Shields, MD, Ocular Oncology iridis/corectopia (20% vs 0%). Other differences relate Service, Ste 1440, Wills Eye Institute, 840 Walnut St, Phila- to features found primarily with iris melanoma such as delphia, PA 19107 ([email protected]). solid tumor compressed in angle (0% vs 46%), iris seed- Author Contributions: Dr C. L. Shields has had full ac- ing of tumor (0% vs 56%), angle seeding of tumor (0% cess to all the data in the study and takes responsibility vs 57%), and extrascleral extension of tumor (0% vs 6%). for the integrity of the data and the accuracy of the data The differentiation of ICE syndrome from iris mela- analysis. noma is important as the main therapeutic strategy for Financial Disclosure: None reported. ICE syndrome–related glaucoma involves open surgical Funding/Support: Support provided by the Eye Tumor procedures,8 and these should be avoided in eyes with Research Foundation (Dr C. L. Shields). melanoma to prevent extraocular tumor spread. The treat- Disclaimer: The funders had no role in the design and ment of iris melanoma depends on many factors includ- conduct of the study; in the collection, analysis, and in- ing tumor size, tumor seeding, and presence of glau- terpretation of the data; and in the preparation, review, coma. Large iris melanomas, particularly those with or approval of the manuscript. seeding and glaucoma, require enucleation or plaque radiotherapy whereas those without seeding or glaucoma can be managed with iridectomy, iridogoniectomy, iri- REFERENCES dogoniocyclectomy, or plaque radiotherapy, depending 17,23,24 on the structures involved. 1. Shields MB, Campbell DG, Simmons RJ. The essential iris atrophies. Am J In summary, ICE syndrome can simulate iris mela- Ophthalmol. 1978;85(6):749-759. noma as is shown in our 71 cases. Both can produce cor- 2. Shields MB. Progressive essential iris atrophy, Chandler’s syndrome, and the ectopia, ectropion iridis, iris distortion, and glaucoma. iris nevus (Cogan-Reese) syndrome: a spectrum of disease. Surv Ophthalmol. 1979;24(1):3-20. Distinguishing features of ICE syndrome include cor- 3. Eagle RC Jr, Font RL, Yanoff M, Fine BS. Proliferative endotheliopathy with iris neal endothelial guttata-like changes, peripheral ante- abnormalities: the iridocorneal endothelial syndrome. Arch Ophthalmol. 1979; rior synechia, iris atrophy, and multidirectional corectopia/ 97(11):2104-2111. ectropion iridis. These are rarely found with iris 4. Yanoff M. Iridocorneal endothelial syndrome: unification of a disease spectrum. Surv Ophthalmol. 1979;24(1):1-2. melanoma. Additional endothelial imaging could assist 5. Wilson MC, Shields MB. A comparison of the clinical variations of the iridocor- in confirming the benign condition of ICE syndrome from neal endothelial syndrome. Arch Ophthalmol. 1989;107(10):1465-1468. the malignant iris melanoma. 6. Laganowski HC, Kerr Muir MG, Hitchings RA. Glaucoma and the iridocorneal endothelial syndrome. Arch Ophthalmol. 1992;110(3):346-350. 7. Teekhasaenee C, Ritch R. Iridocorneal endothelial syndrome in Thai patients: clini- Submitted for Publication: November 27, 2011; final re- cal variations. Arch Ophthalmol. 2000;118(2):187-192. vision received January 25, 2011; accepted January 27, 2011. 8. Doe EA, Budenz DL, Gedde SJ, Imami NR. Long-term surgical outcomes of pa-

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©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 tients with glaucoma secondary to the iridocorneal endothelial syndrome. 17. Shields JA, Shields CL. Melanocytic Tumors of the Iris Stroma: Intraocular Tu- Ophthalmology. 2001;108(10):1789-1795. mors. An Atlas and Textbook. 2nd ed. Philadelphia, PA: Lippincott Williams & 9. Chiou AGY, Kaufman SC, Beuerman RW, Ohta T, Yaylali V, Kaufman HE. Con- Wilkins; 2008:13-36. focal microscopy in the iridocorneal endothelial syndrome. Br J Ophthalmol. 1999; 18. Conway RM, Chua WCT, Qureshi C, Billson FA. Primary iris melanoma: diag- 83(6):697-702. nostic features and outcome of conservative surgical treatment. Br J Ophthalmol. 10. Garibaldi DC, Schein OD, Jun A. Features of the iridocorneal endothelial syn- 2001;85(7):848-854. drome on confocal microscopy. Cornea. 2005;24(3):349-351. 19. Demirci H, Shields CL, Shields JA, Eagle RC Jr, Honavar SG. Diffuse iris mela- 11. Zhang M, Chen J, Liang L, Laties AM, Liu Z. Ultrasound biomicroscopy of Chi- noma: a report of 25 cases. Ophthalmology. 2002;109(8):1553-1560. nese eyes with iridocorneal endothelial syndrome. Br J Ophthalmol. 2006;90 20. Demirci H, Shields CL, Shields JA, Eagle RC Jr, Honavar S. Ring melanoma of (1):64-69. the anterior chamber angle: a report of fourteen cases. Am J Ophthalmol. 2001; 12. Liu YK, Wang IJ, Hu FR, Hung PT, Chang HW. Clinical and specular microscopic 132(3):336-342. manifestations of iridocorneal endothelial syndrome. Jpn J Ophthalmol. 2001; 21. Shields CL, Shields JA, Shields MB, Augsburger JJ. Prevalence and mecha- 45(3):281-287. nisms of secondary intraocular pressure elevation in eyes with intraocular tumors. 13. Levy SG, McCartney ACE, Baghai MH, Barrett MC, Moss J. Pathology of the iri- Ophthalmology. 1987;94(7):839-846. docorneal-endothelial syndrome: the ICE-cell. Invest Ophthalmol Vis Sci. 1995; 36(13):2592-2601. 22. Shields CL, Materin MA, Shields JA, Gershenbaum E, Singh AD, Smith A. Fac- 14. Levy SG, Kirkness CM, Moss J, Ficker L, McCartney AC. The histopathology of tors associated with elevated intraocular pressure in eyes with iris melanoma. the iridocorneal-endothelial syndrome. Cornea. 1996;15(1):46-54. Br J Ophthalmol. 2001;85(6):666-669. 15. Alvarado JA, Underwood JL, Green WR, et al. Detection of herpes simplex viral 23. Shields JA, Shields CL, De Potter P. Local resection of intraocular tumors. DNA in the iridocorneal endothelial syndrome. Arch Ophthalmol. 1994;112 Curr Opin Ophthalmol. 1993;4(3):62-67. doi:10.1097/00055735-199306000 (12):1601-1609. -00011. 16. Shields CL, Shields JA, Materin M, Gershenbaum E, Singh AD, Smith A. Iris mela- 24. Shields CL, Naseripour M, Shields JA, Freire J, Cater J. Custom-designed plaque noma: risk factors for metastasis in 169 consecutive patients. Ophthalmology. radiotherapy for nonresectable iris melanoma in 38 patients: tumor control and 2001;108(1):172-178. ocular complications. Am J Ophthalmol. 2003;135(5):648-656.

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