Congenital Ectropion Uveae and Glaucoma

CLINICOPATHOLOGIC REPORTS, CASE REPORTS, AND SMALL CASE SERIES

SECTION EDITOR: W. RICHARD GREEN, MD

tions of neovascularization in the retinal hemorrhages were not pres- Congenital Ectropion Uveae pathogenesis of CEU are discussed. ent. It was concluded that the and Glaucoma patient had open-angle glaucoma. Report of a Case. In April 2001, a Atropine therapy was discontin- 3-year-old girl was referred to the Wil- ued, and an examination under an- Congenital ectropion uveae (CEU) is liam and Anna Goldberg Glaucoma esthesia accompanied by a possible a rare, nonprogressive condition Service, Wills Eye Hospital, Philadel- filtration procedure in the left eye scarcely mentioned in the ophthal- phia, Pa, by a pediatric ophthalmolo- was scheduled. mic literature. According to its etiol- gist for further management of treat- During the procedure, the IOP ogy, ectropion is classified into 2 ment-resistant glaucoma. The patient was 15 mm Hg OD and 39 mm Hg groups: acquired and congenital. It is had elevated pressure in the left eye, OS, with no intraocular inflamma- believed that the cause of acquired ec- complaints of light sensitivity, ocu- tion. The left pupil was fixed and di- tropion is membranous traction of the lar pain, occasional redness, and a lated, and the horizontal corneal di- iris from secondary causes such as in- “swollen eye.” Ocular history in- ameter measured 13.0 mm OS and flammation and ischemia.1 cluded iris ectropion (ectropion 11.5 mm OD. An abnormal angle According to Dowling et al,2 the uveae) in the left eye and the devel- with an anterior insertion of the iris term congenital ectropion was intro- opment of a spontaneous hyphema. was noted during gonioscopic ex- 3 duced in 1869 by Colsman ; how- One week prior to referral, the intra- amination (Figure 2). Aside from ever, it was later revealed that what ocular pressure (IOP) was 35 mm Hg increased optic nerve cupping (0.6 was really described were flocculi. OS, and IOP-lowering medical treat- cup-disc ratio), the posterior seg- The first authors to actually de- ment was instituted. ment examination results were nor- scribe congenital ectropion were Visual acuity without refractive mal. Surgical trabeculectomy with Wicherkiewicz4 in 1891 and Spiro5 correction was “fix and follow” in adjunctive mitomycin C (0.4 mg/ in 1896. both eyes. External, slitlamp, and go- mL) for 2 minutes was performed, Congenital ectropion uveae con- nioscopic examinations revealed no and a small piece of the iris measur- sists of iris pigment epithelium on evident conjunctival, scleral, or cor- ing 2ϫ1 mm was sent for histo- the anterior surface of the iris, an- neal findings. pathologic examination. terior insertion of the iris, dysgen- The left pupil was fixed and di- Microscopical examination dis- esis of the drainage angle, and glau- lated, and ectropion uveae was evi- closed a folded segment of the iris. coma. Although the actual anomaly dent (Figure 1). Red light reflex A thin layer of iris pigment epithe- is nonprogressive, multiple stud- was present in both eyes and an en- lium, seen both on high (Figure 3) 6-10 ies have linked it with the appear- larged eyecup was noted, although and low magnification, extended ance of progressive open-angle glaucoma due to angle dysgenesis. Most descriptions of CEU2,6-9 have shown a relationship between the presence of ectropion and the even- tual development of glaucoma. Some studies6,9,10 have also associated ectropion uveae with congenital defects and genetic diseases, but re- searchers have not yet verified whether the disease is genetically predetermined or whether it is clearly associated with any of these genetic defects. In this article, a case of CEU in a 3-year-old girl is reported. Histo- pathologic examination of an iris tis- sue specimen obtained during surgical management of glaucoma demonstrated iris neovascularization. Thorough clinical examination revealed no neoplasia. Implica- Figure 1. Nondilated appearance of congenital ectropion uveae.

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Comment. In 1985, Dowling et al2 described 10 patients with CEU, hypoplasia of the iris stroma, irido- trabecular dysgenesis, anterior insertion of the iris root, and glaucoma. No underlying systemic abnormalities were found. It was hypothesized that this syndrome originated from a neural crest cell migration abnormality. Almost all of the patients required surgical inter- vention for IOP control. Ritch et al6 reported 8 cases of CEU. In this series, underlying systemic congenital pathological abnormalities were present in 7 of 8 patients. Neurofibromatosis, Prader- Willi syndrome, Rieger anomaly, and facial hemihypertrophy were found to occur concomitantly with CEU, Figure 2. Intraoperative gonioscopic findings. White arrow indicates congenital ectropion uveae; black arrow, anterior insertion of the peripheral iris. suggesting the possibility of a neural crest cell disorder. Seven of 8 patients developed glaucoma. The present case is unique in that the histopathologic specimen from the iridectomy indicated the presence of a distinct fibrovascular surface membrane covering the anterior aspect of the iris stroma. It is possible that this membrane was responsible for pulling the posterior pigmented layer of the iris anteri- orly, creating the ectropion. This raises the question of whether this membrane together with the previ- H ously noted angle abnormality or the membrane itself is responsible for the decreased aqueous outflow and secondary glaucoma. Also of interest was the presence of intrastromal hemorrhage, which is not believed to have re- Figure 3. Artifactitiously detached monolayer of the iris pigment epithelium rests on the flattened anterior sulted from intraoperative trauma, surface of the iris, which contains many new vessels (arrows). Loculated hemorrhage (H) is present in as well as the suggestion of neovas- ϫ the deeper stroma (hematoxylin-eosin, original magnification 100). cularization on the histopathologic onto the anterior surface of the iris, Descemet membrane, or iris nod- specimen. In such cases, a neo- which was consistent with ectro- ules (Figure 3). plasm must always be excluded, and pion iridis (uveae). Bordering the Three months later, the IOP no neoplasm was found in this pa- area of ectropion iridis, the ante- measured 11 mm Hg OD and 16 tient. This finding correlates with the patient’s history of a spontaneous hy- rior iridic surface appeared flat- mm Hg OS, with a low-lying and phema, which may be similar to the tened. The flattened area was very diffuse bleb in the left eye. The finding of iris neovascularization in regular, suggesting that this re- horizontal corneal diameter was a case of CEU that was described by flected the presence of a delicate, fi- 12.25 mm OS and 11.25 mm OD Roth and Shaffer.10 It also raises the brovascular surface membrane with no Haab striae. The cup-disc question of the cause of the neovas- rather than a compression artifact. ratio had improved to 0.2 OS (from cularization as well as its relation- In some areas, blood was confined 0.6), with a refraction of plano in ship to angle malformation and neu- deep to the surface membrane, and the right eye and −5.0 diopters OS. ral crest cells. It may be possible that there was also presence of iris neo- All of the medications were discon- the primary insult is a vascular fac- vascularization as well as intrastro- tinued, and the only therapeutic tor that secondarily leads to a de- mal hemorrhage. There was no evi- regimen thereafter was patching in fect in neural crest migration, simi- dence of malignancy, ectopic the left eye for 4 h/d. lar to what was seen in an embryonal

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©2006 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 study of the heart.11 These findings However, these tumors can occasion- initial examination (Figure 2B). raise new questions regarding the ally result in severe vision loss. One Eighteen months after the initial mechanisms of the disease. such case is described herein with the examination, the patient returned unusual associated symptom of with further decrease in vision of the Paul J. Harasymowycz, MD sound-induced phosphenes. left eye to light perception. Fundus Demosthenes G. examination showed no change in the Papamatheakis, MD Report of a Case. A 54-year-old white appearance of the melanocytoma Ralph C. Eagle, Jr, MD man sought care because of 5 months (Figure 1C). Some peripheral reti- Richard P. Wilson, MD of blurred vision and decreased pe- nal hemorrhages were noted. The ripheral vision in the left eye. He was height of the tumor remained at 1.6 Correspondence: Dr Harasymo- found to have a pigmented lesion on mm when measured by ultrasonog- wycz, Ophthalmology Research the left optic nerve and referred for raphy. Seven months later, the pa- Unit, Aisle F, CARC, Maisonneuve- further evaluation. He had no his- tient had lost light perception in his Rosemont Hospital, 5415 de tory of eye disease and his medical his- left eye, and diffuse retinal hemor- L’Assomption Blvd, Montreal, Que- tory was noncontributory. rhages were evident throughout the bec, Canada H1T 2M4 (pavloh On examination, his visual acu- fundus with dilated and tortuous @hotmail.com). ity was 20/20 OD and 20/32 OS. The veins, consistent with a central reti- Financial Disclosure: None. pupils were symmetrical with no af- nal vein occlusion (Figure 1D). The ferent pupillary defect. Intraocular height of the mass remained stable as 1. Walton DS. Glaucoma in childhood. In: Al- pressures were 20 mm Hg OD and determined by results of ultrasonog- bert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. 2nd ed. Philadelphia, Pa: WB 21 mm Hg OS. There was no ocular raphy. Over the next 5 months, the Saunders Co; 2000:4408-4415. melanocytosis. The right fundus ap- patient developed neovascular glau- 2. Dowling JL Jr, Albert DM, Nelson LB, Walton peared normal. A 2.5ϫ2-mm darkly coma and, despite panretinal photo- DS. Primary glaucoma associated with irido- trabecular dysgenesis and ectropion uveae. pigmented lesion obscured most coagulation, the eye was enucleated Ophthalmology. 1985;92:912-921. of the left optic disc (Figure 1A). because of pain. The sound-induced 3. Colsman. Papilloma Iridis (physiologische thiera¨hnilche Bildung der Iris). Klin Monatsbl The lesion height was determined to phosphenes persisted for up to 16 Augenheilkd. 1889:7-53. be 1.2 mm by ultrasonography months after enucleation but de- 4. Wicherkiewicz B. Beitrag zur Kenntniss des Ec- (Figure 2A). Fluorescein angiog- creased in frequency. tropion Uveae congenitum. Albrecht von Graefes Arch Ophthalmol. 1891;37:204-207. raphy demonstrated hypofluores- Gross pathologic examination of 5. Spiro G. Ein Fall von Ectropion uveae cence in the area of the lesion, with the enucleated eye revealed a 25 ϫ congenitum. Centralbl Prakt Augenheilkd. 1896; late staining of the visible portion of 25 ϫ 25-mm globe with 2 mm of 20:310-311. 6. Ritch R, Forbes M, Hetherington J Jr, Harri- the optic nerve head (Figure 3). optic nerve attached. Light micro- son R, Podos SM. Congenital ectropion uveae with Automated perimetry showed an in- scopic examination showed partial glaucoma. Ophthalmology. 1984;91:326-331. 7. Mandal AK. Late-onset unilateral primary de- ferior field defect in the left eye. The closure of the anterior segment angle velopmental glaucoma associated with irido- presumptive diagnosis was melano- with peripheral anterior synechiae. trabecular dysgenesis, congenital ectropion cytoma of the optic disc and obser- A neovascular membrane was noted uveae and thickened corneal nerves: a new neural crest syndrome? Ophthalmic Surg Lasers. vation was recommended. on the anterior surface of the iris 1999;30:567-570. Approximately 9 months after the with associated ectropion uveae. 8. Politi F, Sachs R, Barishak R. Neurofibroma- initial examination, the patient noted There were numerous hemorrhages tosis and congenital glaucoma: a case report. Ophthalmologica. 1977;176:155-159. a further decrease in vision in his left throughoutallretinallayers.Pigment- 9. Wolter JR, Butler RG. Pigment spots of the iris eye, pain behind the eye, and flashes laden macrophages were noted in the and ectropion uveae with glaucoma in neurofibromatosis. Am J Ophthalmol. 1963; of light on hearing a loud noise subretinal space with some migration 56:964-973. (sound-induced phosphenes) when into the neural retina. The ganglion 10. Roth H, Shaffer RN. Neurofibromatosis and in the dark. Examination demon- cell layer was attenuated. A heavily glaucoma. In: Bellows JG, ed. Contemporary Ophthalmology: Honoring Sir Stewart Duke- stratedavisualacuityof20/25ODand pigmented tumor occupied most of Elder. Baltimore, Md: Williams & Wilkins; 20/50 OS. There was a left afferent pu- the anterior optic nerve (Figure 5A 1972:180-189. pillary defect. Fundus examination and B). Bleached sections showed 11. Compernolle V, Brusselmans K, Franco D, et al. Cardia bifida, defective heart development and of the left eye showed no significant small nuclei without prominent abnormal neural crest migration in embryos change in the size of the lesion nucleoli(Figure5C).Nomitoseswere lacking hypoxia-inducible factor-1alpha. Car- diovasc Res. 2003;60:569-579. (Figure 1B). Ultrasonography dem- seen. A large area of the retrolaminar onstrated that the lesion’s height had portion of the tumor appeared to increased to 1.6 mm (Figure 2B). be necrotic. Proteinaceous debris Goldmann perimetry showed severe was observed within a larger caliber constriction and an inferior field de- venule, indicative of stasis (Figure 5D Melanocytoma of fectinthelefteye.Magneticresonance and F). A thrombus was noted in a the Optic Nerve imaging showed an enhancing lesion vessel likely to be the central retinal Associated With of the optic nerve, which appeared artery with evidence of recanalization Sound-Induced Phosphenes bright on T1-weighted images (Figure 5E). The optic nerve adjacent (Figure 4). The nerve posterior to to the tumor was severely atrophic. Melanocytomas of the optic disc are the lesion appeared to be atrophic. benign tumors that most often re- Fluorescein angiography demon- Comment. Melanocytoma of the op- main asymptomatic and stable in size. strated no significant change since the tic disc is now commonly recog-

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