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Clinical and histopathologicfindings of iris nevus(Cogan-Reese) syndromeYıldız Ozdemir1, Feyza Onder1, C. Banu Cosar1, Alp Usubutun2

and Gulcan Kural1

Hacettepe University Faculty of Medicine2, Department of Pathology, Ankara,Turkey, Ankara Numune Hospital1, Eye Clinic 1, Ankara, Turkey

ABSTRACT.Purpose: To report a case of Cogan-Reese syndrome.Method: Case report. A 37-year-old man presented with Cogan-Reese syn-drome.Results: Visual acuity was 0.5 in the right eye and 1.0 in the left eye. Therewere corneal edema and pigmented nodules on the anterior surface of the iris,iris atrophy and ectropion uvea in the right eye. The intraocular pressure was42 mmHg in the right eye and there was glaucomatous optic atrophy of the opticdisk. Trabeculectomy with mitomycin C has been performed as the intraocularpressure did not decrease with the maximum medical treatment. Electron micro-scopic examination of the trabeculum and the iris tissue revealed a lot ofmelanocytic cells in the stroma.Conclusion: Trabeculectomy with mitomycin C might be effective in Cogan-Reese cases with glaucoma resistant to medical treatment.

Key words: Iris nevus (Cogan-Reese) syndrome – iridocorneal endothelial syndrome – glaucoma.

Acta Ophthalmol. Scand. 1999: 77: 234–237Copyright c Acta Ophthalmol Scand 1999. ISSN 1395-3907

Iris nevus (Cogan-Reese) syndrome is aclinical entity, characterized by uni-

lateral glaucoma in middle aged individ-uals. The components of the syndromeare iris anomalies such as stromal mat-ting of the iris, nevi on the anterior sur-face of the iris, multiple pigmented irisnodules, and ectropion uveae (Eagle et al.1980).

Iris nevus (Cogan-Reese) syndrome,Chandler syndrome and progressive irisatrophy are altogether named as the iri-docorneal endothelial (ICE) syndromesince they are accepted to represent theclinical spectrum of a single disease.Common pathogenetic mechanisms aretrabecular obstruction, anterior synechiaformation and the development of irisanomalies due to the abnormal prolifer-ation of the corneal endothelial cells. Irisanomalies in the ICE syndrome developsecondary to the endothelial membrane

on its anterior surface and the iris anom-alies vary according to the variations inamount, rate, and the pattern of endo-thelial proliferation. These clinical enti-ties overlap each other during the pro-gression of the disease, so that the differ-ential diagnosis might be difficult(Scheie & Yanoff 1975; Shields et al.1976; Kidd et al. 1988).

In this manuscript, the clinical andelectron microscopic findings of a casewith iris nevus (Cogan-Reese) syndromeis presented.

Case Report37-year-old patient applied to our clinicwith blurred vision and pain persistingfor 10 days in the right eye.

Visual acuity was 0.5 in the right eyeand 1.0 in the left eye. Slit-lamp examina-

tion of the left eye was normal. There wascorneal edema and pigmented nodules onthe anterior surface of the iris in the righteye. The iris nodules were at the nasalquadrant, from the 12 to 5 o’clock posi-tion. They were located on the peripheryof the hypopigmented iris, slightly elev-ated and heteroform (spindle or round)in appearance. The pupil was slightly dis-torted to the 2 o’clock position. Therewas iris atrophy at the 8 o’clock positionand there was ectropion uveae localizedto this area (Fig. 1). The intraocularpressure was 42 mmHg in the right eyeand 16 mmHg in the left eye.

At gonioscopic examination, the anglewas open at all quadrants, and theSchwalbe’s line and the iris processes wereprominent at the 6 o’clock position.There was reticular matting of the per-iphery of the iris in the left eye. In theright eye, there were multiple nodules atthe nasal quadrant, from the 12 to 5o’clock position, between the root of theiris and the scleral spur, and there werepigmentary disturbances at the trabecul-um. The angle was grade 3 at all quad-rants except at the nodular area (Fig. 2).At fundus examination, the left eye wasnormal. In the right eye, there was glau-comatous optic atrophy of the optic diskwith a cup/disk ratio of 0.8 and 0.7 in thehorizontal and vertical meridians, respec-tively. Humphrey automated perimetryexamination revealed normal findings inthe left eye and concentric narrowingreaching to the central 15æ in the righteye.

The patient was given the maximummedical treatment (pilocarpin 2% fourtimes daily, timolol maleate 0.5% twicedaily, acetazolamide 250 mg four timesdaily). Trabeculectomy with mitomycin C

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Fig. 1. Brown-colored, slightly elevated, heteroform nodules on the an- Fig. 2. Nodules at the nasal quadrant of the anterior chamber angleterior iris surface and iris atrophy. between the iris root and the scleral spur and pigmentary disturbances

of the trabeculum.

has been performed as the intraocularpressure did not decrease with the maxi-mum medical treatment. Electron micro-scopic examination of the trabeculumand the iris tissue was performed afterfixation with gluteraldehyde. There werea lot of melanocytic cells in the stroma.Some of these cells were with large cyto-plasms, while some of them were withlarge cytoplasmic filaments. Both of thesecell types included a lot of melanin gran-ules of varying size. (Fig. 3).

One week after the operation, the in-traocular pressure was 30 mmHg. Dur-ing the 2nd and 3rd postoperative weeks,the mean intraocular pressure wasabout 22 mmHg with timolol maleate

Fig. 3. Melanocytic cells with large cytoplasms and long cytoplasmic filaments in the iris stromaand a great number of melanin granules in these cells.

0.5% twice daily and digital massage. Inthe 2nd postoperative month, the trabec-ulectomy bleb was diffusely elevatedand avascular. At slit-lamp examination,there was a pleated silver appearance ofthe corneal epithelium and the stromawas normal. The intraocular pressurewas 14 mmHg in the right eye and 18mmHg in the left eye without medicalantiglaucoma treatment. The visual acu-ity was 0.7 in the right eye and 1.0 inthe left eye.

The intraocular pressure was less than18 mmHg during the follow-up periodfor 26 months. The visual acuity, visualfield and the fundus findings of the pa-tient were stable.

DiscussionIridocorneal (ICE) syndrome consists ofthree similar syndromes: 1. Iris nevus(Cogan-Reese) syndrome, 2. Chandler’ssyndrome and 3. Progressive iris atrophy.ICE syndrome is always unilateral. It isusually seen in middle aged females. It isnot associated with any systemic disease.The patients complain of blurred vision,ocular pain, heterochromia and distortedpupil (Eagle et al. 1980; Scheie & Yanoff1975; Shields et al. 1976; Kidd et al. 1988;Scheie et al. 1976; Laganowski et al.1992).

In the ICE syndrome, there is a pleatedsilver appearance of the posterior cornealsurface, and the iris anomalies rangefrom mild stromal atrophy to the full-thickness hole, sometimes associated withiris nodules (Laganowski et al. 1992). Thechanges of the cornea and the iris, andthe glaucoma are thought to be associ-ated with the proliferation of the cornealendothelium and the basal membrane.Histopathologic examinations revealedthat this membrane is located on the tra-becular network and on the iris (Eagle etal. 1979). Bahn et al. reported that thecorneal endothelium is derived from theneural crest and classified the corneal en-dothelial syndromes on the basis of neu-ral crest origin. According to this classi-fication, ICE syndrome is included in theabnormal crest cell proliferation group.Such a theory might explain the presenceof combined iris pathology and cornealendothelial pathology (Bahn et al. 1979).

Specular microscopy examinations re-vealed large endothelial cells, with a darkarea and a bright central spot, that arelocated at the areas of the cornea that ap-

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pear to be pleated silver. These cells arepathognomonic for ICE syndrome andare called ICE cells. Endothelial anomalymay be without any symptoms or may re-sult in pain or decreased vision by caus-ing corneal edema. The corneal edema ismore pronounced in Chandler’s syn-drome but is less in progressive iris atro-phy and in Cogan-Reese syndrome(Laganowski et al. 1992; Alvarado et al.1986; Lee et al. 1994).

Iris anomalies in ICE cases should bedistinguished from the iris findings of Ax-enfeld-Rieger’s syndrome, aniridia and ir-idoschisis. The differential diagnosis ofthe multiple pigmented iris nodules inCogan-Reese syndrome include neuro-fibromatosis, melanomas (nevus, malig-nant melanoma, tapioca melanoma,melanosis oculi), and the inflammatorynodules seen in lepra, syphilis, tubercu-losis and sarcoidosis. The nodules ofneurofibromatosis are usually bilateral,not well-demarcated and less elevated.There is no associated peripheral anteriorsynechia or pupillary distortion. Themelanomas are also important for thedifferential diagnosis as some eyes withCogan-Reese syndrome were enucleatedfor the false diagnosis of malignant mela-noma as approved by the histopathologicexamination (Shields et al. 1976).

The etiology of the ICE syndrome isunknown. Viruses are suggested to play arole in the cell necrosis and in the trans-formation of the endothelial cells (Alvar-ado et al. 1986). The polymorphonuclearleukocytes among the ICE cells arethought to secret a corneal endothelialmodulation factor and ICE cells arethought to secret an abnormal matrix(Lee et al. 1994).

The ICE syndrome is progressive clin-ically and serious complications such asglaucoma and the corneal decompen-sation occur. In a series of 66 cases withICE syndrome, glaucoma was reported tobe present in 33 (50%) of the cases. It wasrecommended to search for ICE syn-drome in young cases with unilateralglaucoma. Glaucoma was thought to oc-cur as a result of the obstruction of theanterior chamber angle by an abnormalmembrane composed of endothelium-likecells, a descemet-like membrane and theperipheral anterior synechia (Laganowskiet al. 1992).

The differential diagnosis of ICE syn-drome is important as there are manysimilar ocular pathologies. In a series of25 cases with ICE syndrome, the correctdiagnosis of ICE syndrome was made

only in 8 (32%) of the cases at presen-tation. The false initial diagnoses werePosner Schlossman syndrome, chronichypertensive uveitis, Fuchs’ corneal en-dothelial dystrophy, Herpes simplex kera-touveitis, acute and chronic angle closureglaucoma and Reiger’s anomaly(Laganowski et al. 1992).

Cogan and Reese described a case withessential iris atrophy and iris nodules as-sociated with glaucoma, corneal edema,heterochromia, iris surface changes(nodular or matted appearance) and ec-tropion uvea, in 1969. Later, the findingsof iris nevus (Cogan-Reese) syndromehave been described as follows: 1) Nevusat the anterior surface of the iris 2) Pe-ripheral anterior synechia 3) Matted ap-pearance of the iris stroma, loss of iriscrypts 4) Fine iris nodules 5) Ectropionuveae 6) Heterochromia 7) Secondaryglaucoma (Scheie & Yanoff 1975; Shieldset al. 1976).

The most important findings for thediagnosis of iris nevus (Cogan-Reese)syndrome are light microscopy and elec-tron microscopy findings. Electron micro-scopic studies have revealed that the cor-neal endothelial cells are flattened, theyinvolve many endoplasmic reticula andintracytoplasmic filaments of 80–100 Aædiameter, and the descemet membrane isthickened. There is a membrane com-posed of endothelium and abnormalbasal membrane on the trabeculum andthe iris, with many melanocytic cells inthe iris stroma (Eagle et al. 1980;Scheie & Yanoff 1975). The iris atrophyand multiple pigmented nodules were ob-served at slit-lamp and gonioscopic ex-aminations of our case and this is in fa-vour of the diagnosis of iris nevus (Co-gan-Reese) syndrome. The diagnosis wasalso supported by the presence of manymelanocytic cells and the melanin gran-ules in these cells at electron microscopyexamination. The findings related withthe posterior surface of the cornea andthe presence of the membrane on the an-terior iris surface could not be shown be-cause the studied eye was not enucleated.

In the early phases of the ICE syn-drome, the glaucoma due to the obstruc-tion of the outflow routes by the endo-thelial membrane and the peripheral an-terior synechias can be managed bymedical treatment. However, in the latephases of the disease, surgical inter-vention is required in almost all cases.The improvement of glaucoma by con-ventional trabeculectomy in these cases ispoor. Kidd et al. reported the success

rates for the 1st, 2nd and the 3rd trabecu-lectomy operations in a series of 42 caseswith ICE syndrome as 64%, 79% and63%, respectively (Kidd et al. 1988).Laganowski et al. reported the require-ment for more than one surgical inter-vention to be 45% in their ICE syndromeseries. The internal ostium opened by tra-beculectomy might have been later closedby the endothelial membrane and the sy-nechia, and the young age of the patientsmay also add to this. There is prominentsubconjunctival fibrosis in ICE syndromecases and the aggressive inflammatory re-action with development of the scartissue might be the cause of the insuf-ficiency of the bleb (Laganowski et al.1992). Wright et al. reported successfulbleb formation after trabeculectomy withpostoperative subconjunctival 5-fluoro-uracil injection in 4 of the 9 ICE syn-drome cases. They suggested that the lateprogressive endothelial progression mightbe responsible for the unsuccessful oper-ations (Wright et al. 1991).

We performed trabeculectomy with mi-tomycin C in our case as the intraocularpressure did not improve with maximummedical treatment (Pilocarpin 2% fourtimes daily, timolol maleate 0.5% twicedaily, acetazolamide 250 mg four timesdaily). During the postoperative follow-up period of 26 months, the intraocularpressure has been well-controlled.

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Received on August 7th, 1998.Accepted on December 7th, 1998.

Corresponding author:

Yıldız OzdimirAnkara Numune HospitalEye Clinic 1AnkaraTurkey