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.

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.

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.

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.

Current treatments for radiation retinopathy.

BACKGROUND: to review the currently available therapeutic modalities for radiation retinopathy (RR), including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. METHODS: a review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. RESULTS: RR is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intraocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extraocular tumors like cephalic, nasopharyngeal, orbital, and paranasal malignancies. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas are being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. RR has been reported to occur in as many as 60% of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectases, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Regrettably, the management of these eyes remains limited. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor such as bevacizumab, ranibizumab and pegaptanib sodium have been recently used, also with variable results. DISCUSSION: RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. Further large investigative studies are required for developing better therapeutic as well as preventive treatment strategies.

Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: 2-year follow-up.

OBJECTIVE: To evaluate the efficacy and complications of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma. DESIGN: Retrospective review. PARTICIPANTS: 64 patients with juxtapapillary choroidal melanoma. METHODS: Consecutive patients with juxtapapillary choroidal melanomas located within 2 mm of the optic nerve, treated with stereotactic radiotherapy at Princess Margaret Hospital from October 1998 to January 2006, were reviewed for treatment effect and complication rates. RESULTS: Median age was 63 years. Median tumor height was 4.2 mm, and median maximum tumor diameter was 9.8 mm. The prescribed radiation dose was 70 Gy in 5 fractions over 10 days, and the median follow-up was 26 months. After treatment, there was local tumor recurrence in 3 patients, and in 8 patients there was systemic progression. Actuarial rates of local tumor control, metastases, and survival at 26 months were 94%, 12%, and 94%, respectively. Rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 26 months were 28%, 45%, 80%, and 52%, respectively. Enucleation was necessary for 7 patients. CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative with acceptable ocular toxicity rates to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma.

Baseline echographic characteristics of tumors in eyes of patients enrolled in the Collaborative Ocular Melanoma Study: COMS report no. 29.

PURPOSE: To report baseline echographic characteristics of tumors in patients enrolled in the Collaborative Ocular Melanoma Study (COMS) randomized trials, to determine how often these characteristics matched prespecified criteria for choroidal melanoma, to explore associations between echographic variables, and to compare specific echographic characteristics with pathologic characteristics of tumors in enucleated eyes. DESIGN: Retrospective analyses of baseline data from multicenter randomized clinical trials. PARTICIPANTS: Patients enrolled in the COMS large trial or medium tumor trials (N = 2320). METHODS: Standardized echography was used to document selected characteristics of tumors at baseline. Criteria were established to assess the consistency of echographic features with the diagnosis of melanoma. For eyes assigned to enucleation, the echographic diagnosis and evaluation for extraocular extension by the Echography Center were compared with gradings made by the Pathology Center and Pathology Review Committee. MAIN OUTCOME MEASURES: Presence of various echographic and pathologic characteristics. RESULTS: Two thousand forty-three tumors (88%) exhibited low to medium reflectivity (n = 1409), a mushroom shape (n = 101), or both (n = 533). Tumors with apical height > 10 mm were more likely (P<0.001) to have a mushroom shape and less likely to have a posterior location (P<0.001) than less elevated tumors. One thousand five hundred fifty-nine (99.7%) of 1563 tumors judged by echography to be consistent with the diagnosis of melanoma were confirmed by pathology to be choroidal melanoma. For measurable extrascleral tumors < 1.5 mm in height by pathology, the Echography Center graders judged extrascleral extension as possibly present in only 1 of 16 (6%) tumors, compared with 57% (4/7) of eyes with extrascleral extension measuring > or = 1.5 mm in height. CONCLUSIONS: Eighty-eight percent of the tumors in the COMS exhibited features characteristic for melanoma: low to medium reflectivity, the classic mushroom shape, or both. Using additional preset criteria, 96% of tumors exhibited baseline echographic characteristics consistent with the diagnosis of melanoma. Echography graders were able to detect extrascleral nodules > or = 1.5 mm in elevation but not minimally elevated extraocular tumor extension. Clinicians and echographers can use these data to improve their understanding of the echographic features of untreated uveal melanomas.

Ring melanoma of the ciliary body: clinical and ultrasound biomicroscopic characteristics.

BACKGROUND: Diagnosis of ring melanoma is clinically difficult since the mass can remain hidden with standard slit-lamp biomicroscopy. The aim of this study was to evaluate the utility of ultrasound biomicroscopy (UBM) as a diagnostic tool for ring melanoma of the ciliary body. METHODS: This was a retrospective study of 6 eyes of 6 patients at Princess Margaret Hospital, Toronto, Ont., with a diagnosis of ring melanoma of the ciliary body. The tumor extension was measured clinically, gonioscopically, ultrasonographically (by UBM), and pathologically. RESULTS: Since 2000, 6 cases of ring melanoma have been diagnosed at Princess Margaret Hospital: 2 women and 4 men, median age 57 years. Five patients presented as uncontrolled hyperchromic glaucoma (83%). Ciliary body involvement on slit-lamp examination ranged from 60 to 180 degrees. Ciliary body involvement as assessed by UBM ranged from 180 to 300 degrees. Tumor extension according to pathological examination ranged from 210 to 360 degrees. With these measures, the ring melanoma clinical criteria were not filled by 5 patients. INTERPRETATION: UBM is an important tool in determining the extent of ciliary body involvement and classifying these lesions.

Surgical waiting times for ocular and periocular cancer patients in Toronto.

BACKGROUND: The purpose of this study was to evaluate surgical waiting times experienced by intraocular and periocular cancer patients in Toronto and to assess the period of greatest delay between certain stages of ocular cancer care. METHODS: A retrospective chart review was performed on cases of adult patients who underwent surgery between January 2002 and December 2004 for malignant or premalignant tumours of the eye and ocular adnexa. Waiting time intervals were calculated between 5 time points: initial presentation to referring physician or optometrist, date of referral to oculoplastics or ocular oncology, initial assessment, consent date, and surgery date. Total surgical waiting time was the period between the initial presentation and surgery date. RESULTS: The mean total surgical waiting time was 85.93 (standard error [SE] 212.70) days. The 5% trimmed mean total waiting time was 51.07 days. The longest mean total waiting time averaged 94.16 (SE 18.69) days for patients with orbital or lacrimal tumours. For all patients, the interval of greatest delay was between initial assessment and consent (according to means) or between referral and initial assessment (according to 5% trimmed means). For patients with lid, brow, or conjunctival tumours the interval of greatest delay was between referral and initial assessment, and for those with orbital, lacrimal, or intraocular tumours it was between initial assessment and consent. INTERPRETATION: By measuring the period between consent and surgery, the Ontario government is not measuring the interval of greatest delay in ocular cancer care. The wait-time registry may benefit from including data from patients with periocular tumours.

Small ciliary body tumors: ultrasound biomicroscopic assessment and follow-up of 42 patients.

PURPOSE: Detecting and following small tumors of the ciliary body is a particular challenge because of their location. Recently high-frequency ultrasound biomicroscopy (UBM) has been used to assist in this task. The aim of this study was to evaluate this subset of small ciliary body tumors through the use of UBM. DESIGN: Retrospective, noncomparative case series. METHODS: Forty-two patients with small ciliary body tumors (less than 4 mm) from our institution were included in the study with a median follow-up of 4.3 years. UBM was used to assess tumor characteristics including height, location, and internal and external features. The data were collected longitudinally, and statistical analysis was performed. RESULTS: Median initial tumor height was 2.05 mm (range 1.1 to 3.8 mm) as measured by UBM. By 5 years after diagnosis, five tumors (12%) exhibited growth. The overall mean growth rate was 0.026 mm per year (P = .00007). The most rapid period of growth was in the first year after diagnosis (growth rate 0.128 mm per year), after which the mean tumor size appeared to stabilize. CONCLUSIONS: UBM is a valuable tool for detecting and following small ciliary body tumors (less than 4 mm), as these lesions may go undetected by other methods. Despite the potential for local extension into the iris or choroid, few of the tumors in this study exhibited growth, suggesting that many of these tumors can be managed conservatively. UBM can be used to assess various internal tumor features; however, arriving at a specific diagnosis without histologic correlation is difficult.

Primary intraosseous hemangioma of the orbit: an unusual presentation of an uncommon tumor.

CASE REPORT: An asymptomatic patient was referred for assessment of an intraocular amelanotic mass in her left eye. Examination showed a mass effect in the inferior location at the 5 o'clock position. This abnormality was defined with ultrasound biomicroscopy and standard ultrasound, but because the appearance was not typical of a melanoma or other choroidal infiltrate, magnetic resonance images and computed tomograms of the orbits were obtained, identifying an extraocular mass arising from the zygomatic rim. Results of a biopsy reported an intraosseous hemangioma. COMMENTS: The diagnosis of intraosseous hemangioma, because of its low incidence and unusual manner of presentation, can be challenging. Computed tomography and biopsy are helpful in making a definitive diagnosis.

Extrascleral extension in association with ciliochoroidal melanoma: ultrasound biomicroscopy with histopathological correlation.

CASE REPORT: We present the case of a 71-year-old man with a melanoma arising from the ciliary body and extending into the choroid. Ultrasound biomicroscopy (UBM) revealed connection via an emissary canal to a subconjunctival nodule. Although evaluation for metastasis was negative at the time of diagnosis, multiple hepatic metastatic deposits were found 2 years post-enucleation. COMMENTS: It is crucial to identify the presence of scleral invasion and extrascleral extension for proper management planning in patients with choroidal melanomas. This case demonstrates that UBM is an accurate and useful tool for characterizing the morphologic pattern of scleral invasion of intraocular tumours.

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.

Stereotactic radiotherapy in the treatment of juxtapapillary choroidal melanoma: preliminary results.

PURPOSE: To evaluate the preliminary results of stereotactic radiotherapy in the management of patients with juxtapapillary choroidal melanoma. METHODS & MATERIALS: A retrospective, consecutive case series of 28 patients with choroidal melanoma located within 2 mm of the optic nerve who were treated with stereotactic radiotherapy at Princess Margaret Hospital, Toronto, between October 1998 and May 2001. RESULTS: Median age was 62 years. Median tumor height was 4.6 mm and median maximum tumor diameter was 9.4 mm. The prescribed radiation dose was 70 Gy in five fractions over 10 days and median follow-up was 18.5 months. Posttreatment, 2 patients developed local tumor regrowth and 3 patients developed liver metastases. Actuarial rates of local tumor control, metastases, and survival at 18 months were 96%, 10%, and 94%, respectively. Actuarial rates of radiation-induced neovascular glaucoma, cataract, retinopathy, and optic neuropathy at 18 months were 20%, 29%, 30%, and 37%, respectively. A higher radiation dose to the lens was associated with an increased risk of cataract (p = 0.02). CONCLUSIONS: Stereotactic radiotherapy offers a noninvasive alternative to enucleation and brachytherapy in the management of juxtapapillary choroidal melanoma. However, further efforts are needed to optimize local tumor control and minimize radiation-induced complications.

Anterior chamber depth in plateau iris syndrome and pupillary block as measured by ultrasound biomicroscopy.

PURPOSE: To quantitatively analyze the anterior chamber depth (ACD) in patients with pupillary block and plateau iris syndrome. DESIGN: Retrospective, consecutive, observational case series. METHODS: We measured the ACD in 318 eyes of 318 patients who had been diagnosed by ultrasound biomicroscopy as having either pupillary block or plateau iris syndrome. Pupillary block patients were all preiridotomy and plateau iris patients were all postiridotomy. Anterior chamber depth was measured axially from the internal corneal surface to the lens surface using the ultrasound instrument's internal measuring capability. RESULTS: The mean ACD in patients with plateau iris syndrome (n = 181) was significantly smaller than the hypothesized normal ACD (2.04 +/- 0.30 mm vs 3.0 mm, P =.0001). The mean ACD in patients with pupillary block (n = 137) was also significantly smaller than the hypothesized normal ACD (2.17 +/- 0.30 mm vs 3.0 mm, P =.0001). The mean ACD in patients with plateau iris syndrome was significantly smaller than the ACD in patients with pupillary block (2.04 +/- 0.30 mm vs 2.17 +/- 0.30 mm, P =.001). CONCLUSIONS: Review of the literature suggests that patients with plateau iris have a normal or deeper axial ACD compared with pupillary block. This study found that the ACD associated with plateau iris syndrome is shallower than normal and also shallower than in pupillary block.

Ciliary body melanoma: a special challenge.

Although there is little doubt that the delayed recognition of ciliary body melanoma has a bearing on patient management and ultimate survival, the most compelling issues that face the clinician treating this neoplasm relate to the metastatic patterns and mechanisms of the disease. Several aspects of diagnosis and management of this tumour provide a unique challenge to the clinician. Ciliary body melanoma can remain clinically inapparent to the patient as well as to the clinician during its formative period. In management, tumour characteristics, including anterior and posterior margins, are more readily visualized with ultrasound biomicroscopy (UBM) than with other imaging techniques. UBM can provide valuable information when considering intervention, including biopsy, resection or plaque radiotherapy. Management depends on tumour size, intraocular involvement, patient preference and the presence or absence of systemic manifestations.

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.