Evaluation of the characteristics of primary iridociliary cysts using ultrasound biomicroscopy at a tertiary care centre.

OBJECTIVE: To evaluate the ultrasound biomicroscopic characteristics of primary iridociliary cysts presenting to a Canadian tertiary care centre. DESIGN: Retrospective study. PARTICIPANTS: A total of 189 patients (212 eyes) referred to the Sinai Health System (Toronto) for suspected iris abnormalities. METHODS: Clinical records of patients referred between March 2016 and October 2019 were reviewed. All patients were evaluated and received a diagnosis of an iridociliary cyst using ultrasound biomicroscopy (UBM). Data were collected for age, sex, involvement (iris vs ciliary body), laterality, size, and location on initial examination and subsequent follow-up. RESULTS: Of the 189 patients (212 eyes) with iridociliary cysts, more were female (65.1%) versus male (34.9%). The highest incidence occurred in females aged 21-30 years (13.2%). The iris pigment epithelium was involved in 84.4%, and only the ciliary body was involved in 3.8%. Both the iris pigment epithelium and the ciliary body were involved in 10.8%. The size of the cysts ranged between 0.5 and 4.41 mm in diameter. Cysts greater than 1 mm in diameter occurred in 78.7%, and 86.8% of cysts occurred unilaterally. Twelve percent were multicystic, and 8.5% were multiloculated, with 1% exhibiting both features. Twenty-three eyes (12.2%) were reviewed at 1 year of follow-up with UBM. Stable iridociliary cysts with no appreciable change in size were seen in 73.9% (n = 17). Iridociliary cyst growth was noted at 4 months in 1 patient. CONCLUSION: Information regarding iridociliary cysts is not easily available in the literature. UBM is a helpful clinical tool in the evaluation of iris abnormalities. Iridociliary cysts tend to be stable and compatible with a low rate of complications.

Patients presenting with metastases: stage IV uveal melanoma, an international study.

OBJECTIVE: To analyse ocular and systemic findings of patients presenting with systemic metastasis. METHODS AND ANALYSIS: It is an international, multicentre, internet-enabled, registry-based retrospective data analysis. Patients were diagnosed between 2001 and 2011. Data included: primary tumour dimensions, extrascleral extension, ciliary body involvement, American Joint Committee on Cancer (AJCC)-tumour, node, metastasis staging, characteristics of metastases. RESULTS: Of 3610 patients with uveal melanoma, 69 (1.9%; 95% CI 1.5 to 2.4) presented with clinical metastasis (stage IV). These melanomas originated in the iris, ciliary body and choroid in 4%, 16% and 80% of eyes, respectively. Using eighth edition AJCC, 8 (11%), 20 (29%), 24 (35%), and 17 (25%) belonged to AJCC T-categories T1-T4. Risk of synchronous metastases increased from 0.7% (T1) to 1.5% (T2), 2.6% (T3) and 7.9% (T4). Regional lymph node metastases (N1a) were detected in 9 (13%) patients of whom 6 (67%) had extrascleral extension. Stage of systemic metastases (known for 40 (59%) stage IV patients) revealed 14 (35%), 25 (63%) and 1 (2%) had small (M1a), medium-sized (M1b) and large-sized (M1c) metastases, respectively. Location of metastases in stage IV patients were liver (91%), lung (16%), bone (9%), brain (6%), subcutaneous tissue (4%) and others (5%). Multiple sites of metastases were noted in 24%. Compared with the 98.1% of patients who did not present with metastases, those with synchronous metastases had larger intraocular tumours, more frequent extrascleral extension, ciliary body involvement and thus a higher AJCC T-category. CONCLUSIONS: Though higher AJCC T-stage was associated with risk for metastases at diagnosis, even small T1 tumours were stage IV at initial presentation. The liver was the most common site of metastases; however, frequent multiorgan involvement supports initial whole-body staging.

Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease.

OBJECTIVE: To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD). DESIGN: Cohort study. PARTICIPANTS: Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010. METHODS: Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG. RESULTS: Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull's-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity. CONCLUSIONS: High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity.

Bilateral multifocal choroidal melanosis: a report of two cases.

Flat choroidal pigmented lesions have few differential diagnoses but encompass a wide range of clinical presentations. The authors report two cases of bilateral multifocal choroidal hyper-pigmented patches discovered in asymptomatic patients. Fluorescein angiography showed a normal pattern without blockage in the hyperpigmented areas with an otherwise normal choroidal vascular architecture. Optical coherence tomography with enhanced depth imaging demonstrated normal choroidal thickness and structure in the hyperpigmented areas. These cases may represent an atypical presentation of previously described bilateral isolated choroidal melanocytosis or a different clinical entity. Histopathological evidence and longer follow-up of these patients and patients with isolated choroidal melanocytosis may elucidate the best descriptive term for this unusual condition.

A comparison between ¹²5Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma.

AIMS: To compare the treatment efficacy and radiation complications between (125)Iodine brachytherapy and stereotactic radiotherapy in the management of juxtapapillary choroidal melanoma. METHODS: Consecutive juxtapapillary melanoma patients treated with radiotherapy were included. Patients were divided into two cohorts: patients treated with (125)Iodine brachytherapy and patients with stereotactic radiotherapy. Comparison included the rates postradiotherapy local recurrence, secondary enucleation, metastasis and radiotherapy complications. Kaplan-Meier estimates were used to determine the actuarial rates, and logrank test to compare between the estimates. RESULTS: We included 94 patients with juxtapapillary melanoma treated with radiotherapy. The brachytherapy cohort included 30 patients and stereotactic radiotherapy was 64. The median follow-up was 46 months in both cohorts. No statistically significant differences existed between the two cohorts on comparing pretreatment clinical data and tumour characteristics. On comparing treatment efficacy, the actuarial rates at 50 months for tumour recurrence were 11% and 7% (p=0.61), secondary enucleation was 11% and 21% (p=0.30) and for metastasis were 4% and 16% (p=0.11), respectively. On comparing treatment complications, the actuarial rates at 50 months for cataracts were 62% and 75% (p=0.1), for neovascular glaucoma 8% and 47% (p=0.002), for radiation retinopathy 59% and 89% (p=0.0001), and for radiation papillopathy 39% and 74% (p=0.003), respectively. CONCLUSIONS: Both (125)Iodine brachytherapy and stereotactic radiotherapy demonstrate comparable efficacy in the management of juxtapapillary choroidal melanoma. However, stereotactic radiotherapy shows statistically significant higher radiation-induced ocular morbidities at 4 years postradiotherapy.

Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child.

AIMS: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis. METHODS: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome. RESULTS: The tumour had predominantly epithelioid histology. Karyotype analysis showed none of the poor prognosis features normally associated with uveal melanoma. single nucleotide polymorphism analysis revealed no imbalance at chromosome 3. Gene expression profiling indicated low risk disease. CONCLUSIONS: We report a child remaining relapse-free 6 years after diagnosis of a very rare uveal melanoma, with poor prognosis epithelioid histology, but gene expression profiling that accurately predicted low risk disease.

Ultrasound biomicroscopy of the ciliary body in ocular/oculodermal melanocytosis.

PURPOSE: To describe the ultrasound biomicroscopy (UBM) findings of the ciliary body in patients with ocular/oculodermal melanocytosis. DESIGN: Retrospective observational case series study. METHODS: A retrospective chart and imaging database review was conducted for patients with unilateral ocular/oculodermal melanocytosis who underwent UBM examination at the Ocular Oncology Clinic of Princess Margaret Hospital. Radial images of the ciliary body at the 3-, 6-, 9-, and 12-o'clock positions were obtained in both eyes. UBM characteristics included ciliary body thickness and reflectivity. The eye with ocular/oculodermal melanocytosis was compared with the contralateral unaffected eye as a control. Statistical significance was analyzed with Student t test. RESULTS: Twelve patients were included. All patients showed unilateral diffuse pigmentation involving episclera and anterior chamber angle. The iris showed diffuse pigmentation in 10 cases and sectorial in 2. Mean ciliary body thickness of the affected eyes was 0.581 ± 0.058 mm (range 0.489-0.744) compared with 0.475 ± 0.048 mm (range 0.406-0.622) in the contralateral eye, which was found to be a statistically significant difference (P < .001). The affected ciliary body showed hyperreflectivity when compared with the unaffected eye. All affected eyes were graded as medium to high reflectivity compared with the unaffected eyes that showed a medium to medium/low reflectivity. CONCLUSION: Ciliary body involvement in ocular/oculodermal melanocytosis presents as increased thickness and higher ultrasound reflectivity on UBM when compared with the unaffected eye. UBM is helpful in imaging clinically undetectable areas of melanocytosis involving the ciliary body.

Referral patterns of intraocular tumour patients to a dedicated Canadian ocular oncology department.

OBJECTIVE: Intraocular tumours are uncommon lesions requiring comprehensive management at tertiary referral centers. This study analyzes referral patterns of intraocular tumours, accuracy of referral diagnosis, and modes of treatment provided for patients at a dedicated Canadian Ocular Oncology Department. DESIGN: Retrospective chart review. PARTICIPANTS: A total of 1050 new patient referrals of intraocular tumours to the department of Ocular Oncology at Princess Margaret Hospital (PMH) between 2005 and 2008 inclusive. METHODS: Data collected for each patient included demographics, referral diagnosis, final diagnosis, and treatment provided or recommended. Home address postal codes were used to determine patients' geographical distance to PMH. RESULTS: Most patients originated from Ontario (81.5%) followed by Alberta (7.1%) with a median age of referral at 61 years old. The most common referral diagnoses were unknown diagnosis (47.6%), uveal melanoma (26.9%), and nevus (18.9%). After evaluation at PMH, uveal nevus was the most common final diagnosis (39.7%) followed by melanoma (39.2%). The referring physicians correctly diagnosed 48.5% of total melanomas. The proportion of melanoma diagnosis relative to total referrals by province ranged from 29.6% for Ontario to 100% for Quebec. Distance from the patient's address to PMH was <200 kilometres in 64.5% of patients and >1000 kilometres in 21.6% of patients. CONCLUSIONS: The limited accuracy of referral diagnoses and increased proportion of melanoma referrals from greater distances demonstrates the need for increased knowledge in ocular oncology, improvement of eye cancer care facilities at the referral base, and/or the implementation of tele-ophthalmology.

Collaborative Ocular Oncology Group report number 1: prospective validation of a multi-gene prognostic assay in uveal melanoma.

PURPOSE: This study evaluates the prognostic performance of a 15 gene expression profiling (GEP) assay that assigns primary posterior uveal melanomas to prognostic subgroups: class 1 (low metastatic risk) and class 2 (high metastatic risk). DESIGN: Prospective, multicenter study. PARTICIPANTS: A total of 459 patients with posterior uveal melanoma were enrolled from 12 independent centers. TESTING: Tumors were classified by GEP as class 1 or class 2. The first 260 samples were also analyzed for chromosome 3 status using a single nucleotide polymorphism assay. Net reclassification improvement analysis was performed to compare the prognostic accuracy of GEP with the 7th edition clinical Tumor-Node-Metastasis (TNM) classification and chromosome 3 status. MAIN OUTCOME MEASURES: Patients were managed for their primary tumor and monitored for metastasis. RESULTS: The GEP assay successfully classified 446 of 459 cases (97.2%). The GEP was class 1 in 276 cases (61.9%) and class 2 in 170 cases (38.1%). Median follow-up was 17.4 months (mean, 18.0 months). Metastasis was detected in 3 class 1 cases (1.1%) and 44 class 2 cases (25.9%) (log-rank test, P<10(-14)). Although there was an association between GEP class 2 and monosomy 3 (Fisher exact test, P<0.0001), 54 of 260 tumors (20.8%) were discordant for GEP and chromosome 3 status, among which GEP demonstrated superior prognostic accuracy (log-rank test, P = 0.0001). By using multivariate Cox modeling, GEP class had a stronger independent association with metastasis than any other prognostic factor (P<0.0001). Chromosome 3 status did not contribute additional prognostic information that was independent of GEP (P = 0.2). At 3 years follow-up, the net reclassification improvement of GEP over TNM classification was 0.43 (P = 0.001) and 0.38 (P = 0.004) over chromosome 3 status. CONCLUSIONS: The GEP assay had a high technical success rate and was the most accurate prognostic marker among all of the factors analyzed. The GEP provided a highly significant improvement in prognostic accuracy over clinical TNM classification and chromosome 3 status. Chromosome 3 status did not provide prognostic information that was independent of GEP.

Clinical and ultrasound biomicroscopy features associated with growth in iris melanocytic lesions.

PURPOSE: To determine the clinical and ultrasound biomicroscopy (UBM) features associated with growth in iris melanocytic lesions. STUDY DESIGN: Retrospective case series analysis. METHODS: We included all iris melanocytic lesions that were monitored between January 2005 and November 2009. At the end of the analysis, 44 eyes of 44 patients were included in the final analysis. The clinical features analyzed were: iris color, largest base diameter, radial location of the lesion epicenter, circumferential location of the lesion epicenter, lesion configuration, lesion pigmentation, intrinsic vascularity within the lesion, presence of associated pigmentation, the impact on the pupil, presence of iris atrophy, and lesion-induced localized cataracts. The UBM features included lesion thickness, presence of corneal touch, presence of surface plaque, internal structure, and internal reflectivity. Regression analysis was performed to define the features associated with growth. RESULTS: Twenty-three percent of the lesions showed documented growth. Mean follow-up was 21.4 months (range: 10-48). Clinical features associated with growth were a large basal diameter at baseline (P = .004) and inferior location (P = .004). UBM features associated with growth were: a greater baseline thickness (P = .01), presence of corneal touch (P = .007), an irregular internal structure (P = .0001), and the presence of dots and linear streaks (P < .0001). Clinical features that were not associated with growth were the radial location of the lesion in the iris (P > .999), lesion configuration (P > .999), lesion pigmentation (P > .999), the presence of pigment dispersion (P = .70), iris freckles (P = .15), corectopia (P > .999), ectropion (P > .999), and intrinsic vascularity (P = .70). UBM features not associated with growth were the presence of a surface plaque (P = .07) and the internal reflectivity (P = .77). CONCLUSION: Substantial growth in iris melanocytic lesions is associated with original larger basal diameter and inferior lesion location. On UBM growth is associated with greater original thickness, presence of corneal touch, and an irregular internal structure. Presence of these features could modify the frequency of observation of those lesions.

Multimodal fundus imaging in choroidal osteoma.

PURPOSE: To describe the morphologic features of calcified and decalcified choroidal osteomas using multimodal imaging and correlate these findings with a previous histopathologic study. DESIGN: Retrospective observational case series. METHODS: Three patients with choroidal osteoma underwent complete ophthalmologic examination, fundus photography, and multimodal fundus imaging, including Fourier-domain optical coherence tomography (FD-OCT) and blue-light fundus autofluorescence (bAF). RESULTS: FD-OCT imaging of calcified tumors revealed a distinctive latticework pattern of reflectivity resembling the spongy bone structure seen histopathologically. On bAF the fluorescence was relatively well preserved overlying calcified tumors. In decalcified areas 2 patterns of reflectivity were identified: the first consisted of areas of relative hyperreflectivity with a lamellar appearance while the second was characterized by heterogeneous, hyperreflective, mound-like irregular areas associated with some posterior optical shadowing. Decalcified tumor areas had reduced overall fluorescence on bAF. CONCLUSION: FD-OCT demonstrated different reflectivity patterns in both calcified and decalcified portions of the choroidal osteoma, which may correspond to different stages of tumor evolution. A distinctive latticework pattern of reflectivity similar to spongy bone was seen in calcified tumors. These observations improve our knowledge of the in vivo structure of choroidal osteomas and may have implications for the diagnosis and management of this tumor.

Intraocular extension of conjunctival invasive squamous cell carcinoma after pterygium surgery and cataract extraction.

OBJECTIVES: Conjunctival squamous dysplasia can often be confused with pterygium and pinguecula. Incomplete excision of dysplastic tissue can lead to recurrence and rarely intraocular invasion. This study describes two cases in which invasive squamous cell carcinoma (SCC) of the conjunctiva was originally partially resected as pterygium and eventually required enucleation for intraocular invasion. METHODS: In this clinicopathologic small case series, two cases of intraocular SCC managed at a single tertiary ocular oncology institution are described. Clinical features, pathologic characteristics, and relevant imaging are described. RESULTS: In both cases, incomplete excision of conjunctival SCC was followed by rapid regrowth of the conjunctival lesion and signs of intraocular inflammation. An intraocular mass within the substance of the ciliary body was identified using ultrasound biomicroscopy in both the cases. Enucleation was performed. Pathologic features were typical to SCC. CONCLUSIONS: Intraocular spread on conjunctival SCC occurs only rarely but tends to follow recurrence of the conjunctival lesion after attempted excision. Modes of invasion may include direct invasion through sclera, along the tract of the anterior ciliary vessels, or inoculation through intraocular surgery incision.

Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study.

OBJECTIVE: To collaborate with multiple centers to identify representative epidemiological, clinical, and pathologic characteristics of melanoma of the iris. This international, multicenter, Internet-assisted study in ophthalmic oncology demonstrates the collaboration among eye cancer specialists to stage and describe the clinical and pathologic characteristics of biopsy-proven melanoma of the iris. METHODS: A computer program was created to allow for Internet-assisted multicenter, privacy-protected, online data entry. Eight eye cancer centers in 6 countries performed retrospective chart reviews. Statistical analysis included patient and tumor characteristics, ocular and angle abnormalities, management, histopathology, and outcomes. RESULTS: A total of 131 patients with iris melanoma (mean age, 64 years [range, 20-100 years]) were found to have blue-gray (62.2%), green-hazel (29.1%), or brown (8.7%) irides. Iris melanoma color was brown (65.6%), amelanotic (9.9%), and multicolored (6.9%). A mean of 2.5 clock hours of iris was visibly involved with melanoma, typically centered at the 6-o'clock meridian. Presentations included iritis, glaucoma, hyphema, and sector cataract. High-frequency ultrasonography revealed a largest mean tumor diameter of 4.9 mm, a mean maximum tumor thickness of 1.9 mm, angle blunting (52%), iris root disinsertion (9%), and posterior iris pigment epithelium displacement (9%). Using the American Joint Commission on Cancer-International Union Against Cancer classification, we identified 56% of tumors as T1, 34% of tumors as T2, 2% of tumors as T3, and 1% of tumors as T4. Histopathologic grades were G1-spindle (54%), G2-mixed (28%), G3-epithelioid (5%), and undetermined (13%) cell types. Primary treatment involved radiation (26%) and surgery (64%). Kaplan-Meier analysis found a 10.7% risk of metastatic melanoma at 5 years. CONCLUSIONS: Iris melanomas were most likely to be brown and found in the inferior quadrants of patients with light irides. Typically small and unifocal, melanomas are commonly associated with angle blunting and spindle cell histopathology. This multicenter, Internet-based, international study successfully pooled data and extracted information on biopsy-proven melanoma of the iris.

Cancer-associated nummular loss of RPE: expanding the clinical spectrum of bilateral diffuse uveal melanocytic proliferation.

This report describes a case of cancer-associated nummular retinal pigment epithelium loss associated with uterine cancer. The patient had progressive visual loss despite treatment with plasmapheresis, intravenous immunoglobulin, and local injection of corticosteroids. Clinical deterioration was corroborated by extension of the areas of retinal pigment epithelium loss, progression of cataracts, and growth of pigmented choroidal and iris lesions. Previously published cases of cancer-associated nummular retinal pigment epithelium loss did not describe the presence of cataracts or uveal melanocytic lesions. This case expands the clinical spectrum of bilateral diffuse uveal melanocytic proliferation.

Ultrasound biomicroscopic imaging of iris melanoma: a clinicopathologic study.

PURPOSE: To demonstrate the correlation of ultrasound biomicroscopy (UBM) features of iris melanoma with histopathology. DESIGN: Retrospective analysis of medical records. METHODS: The medical records of patients that underwent surgery for iris melanoma at the Princess Margaret Hospital, University of Toronto, from June 1990 to October 1998 were reviewed. The clinical features, as well as the UBM findings prior to surgical intervention, were evaluated. The anatomic features noted on UBM were correlated with histopathologic features seen in the surgical specimens. RESULTS: Fourteen cases met the inclusion criteria and were included in the final analysis. The ultrasound acoustic characteristics showed a broad spectrum of findings among iris melanomas. Tumor acoustic parameters correlated well with histologic features, including tumor vascularity, surface plaque, extrascleral extension, ciliary body involvement, and integrity of iris pigment epithelium. CONCLUSIONS: UBM is a useful imaging technique for the in vivo assessment of primary iris melanoma and can provide detailed imaging of the tumor's interface with the angle structures. The preoperative assessment of these tumors by UBM may aid the surgeon in choosing the most appropriate technique to ensure total removal.