Orbital radiation therapy for Graves' ophthalmopathy: measuring clinical efficacy and impact.

PURPOSE: Graves' ophthalmopathy (GO) is an autoimmune condition primarily managed with prolonged courses of glucocorticoids, which can be associated with significant side effects. Orbital radiation therapy (RT) is an alternative treatment that has shown variable efficacy in improving orbital and visual symptoms. In this study, the therapeutic benefit of RT was evaluated in terms of patient's ability to taper their corticosteroid requirements, which may better reflect the proposed mechanism of RT and provide a clinically relevant response endpoint. METHODS AND MATERIALS: This is a retrospective review of consecutive patients treated with orbital RT for GO between 2000 and 2010 at a single tertiary hospital with a dedicated ocular radiation therapy clinic. The primary measure of treatment response was defined as the ability to taper glucocorticoids following RT without any further exacerbation of orbitopathy symptoms. Additional endpoints including ocular symptoms (diplopia, proptosis, visual acuity, extraocular movement) and need for surgical intervention were reported. RESULTS: Of 86 eligible patients, with a mean follow-up of 9.3 months, 81 (94%) patients responded to RT. Of patients taking corticosteroids at baseline, 91% were able to taper off corticosteroids completely and the remaining patients had decreased their doses by 83%. Diplopia, visual acuity, and extraocular movements improved in 29%, 81%, and 58% of patients, respectively. The median reduction in proptosis was 2.5 mm and 2 mm in the left and right eyes, respectively (range, -18 mm to 23 mm). CONCLUSIONS: Orbital RT is a generally well-tolerated treatment that helps minimize the dose and duration of corticosteroid therapy for patients with GO while improving ocular symptoms, including proptosis and diplopia. Prospective research should consider using corticosteroid requirement as a measure of response to orbital RT for GO.

Unusual orange-colored choroidal metastases.

PURPOSE: To report the clinical and paraclinical features of two patients with orange- colored choroidal metastases in whom the primary cancers have not previously been associated with such lesions. CASE REPORT: Orange-colored choroidal lesions were detected on the fundus examination of one patient with metastatic small cell neuroendocrine tumor of the larynx and oropharynx, and in another subject with metastatic alveolar soft part sarcoma of the leg. Although ultrasonographic characteristics of the choroidal masses were comparable to those of choroidal hemangiomas, fluorescein angiography revealed delayed initial fluorescence along with minimal fluorescence in subsequent phases of the angiogram which were in clear distinction from the earlier appearing and progressively intense fluorescence observed with circumscribed choroidal hemangiomas. CONCLUSION: Small cell neuroendocrine tumors and alveolar soft part sarcomas should be considered among the differential diagnoses for orange-colored choroidal metastases. Identifying these choroidal lesions could facilitate localizing the occult primary tumor. Fluorescein angiography may differentiate a unifocal orange choroidal metastasis from a circumscribed choroidal hemangioma.

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.

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.

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.

Neovascular glaucoma after stereotactic radiotherapy for juxtapapillary choroidal melanoma: histopathologic and dosimetric findings.

PURPOSE: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. METHODS AND MATERIALS: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. RESULTS: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. CONCLUSIONS: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

Orbital lymphoma presenting with choroidal detachments.

This report describes a case of orbital B-cell lymphoma of extranodal marginal cell type with atypical clinical and radiographic features. This patient presented with choroidal effusion and optic disk swelling of the right eye. A CT scan revealed an intraconal mass surrounding the optic nerve and indenting the globe. A right orbitotomy with biopsy of the mass was performed. Histologic and immunohistochemical analysis confirmed a diagnosis of extranodal marginal zone B-cell lymphoma. This is the first case of primary orbital lymphoma presenting with choroidal effusion described in the literature.

Management of iris melanomas with 125Iodine plaque radiotherapy.

PURPOSE: To report the experience of the Princess Margaret Hospital/University Health Network with the treatment of iris melanoma (IM) with (125)Iodine plaque brachytherapy. DESIGN: Retrospective noncomparative case series. METHODS: All cases of IM submitted to (125)Iodine plaque radiotherapy were included. Patients' demographic, clinical, management, and follow-up data were reviewed. Outcome measures included rates of tumor control, eye preservation, systemic metastases, and brachytherapy-related complications. RESULTS: Fourteen IMs were included in the study. All patients had blue/green irises. Mean largest basal dimension and thickness were 7.1 +/- 2.1 mm (range, 4.0 to 11.5 mm) and 2.2 +/- 0.8 mm (range, 1.0 to 3.5 mm), respectively. Ten patients (71%) had seeding and 2 (14%) had glaucoma at presentation. Median follow-up was 26.6 +/- 19.5 months (range, 6 to 72 months). Tumor control was achieved in 100% of the cases and no eye was enucleated because of radiation-induced complications. At last visit, all patients were alive and free of metastasis. Final visual acuity was the same as or better than before treatment in 9 patients (75%). Cataract was the most common complication (8; 75%), followed by persistent glaucoma (2; 17%) and anterior uveitis (1; 8%). No other significant complication was seen during the follow-up period. CONCLUSIONS: Plaque radiotherapy is a safe and effective conservative treatment option for IM, although cataract is a common, yet treatable, complication. This treatment scheme circumvents an intraocular procedure and may avoid the dissemination of malignant cells, and provides a margin of safety in the treatment of clinically undetectable disease.

Management of ciliary body melanoma with iodine-125 plaque brachytherapy.

OBJECTIVE: Because ciliary body melanoma often defies early diagnosis, and its treatment is controversial, we report our experience with the clinical presentation and management of ciliary body melanoma, treated with iodine-125 plaque brachytherapy. STUDY DESIGN: A retrospective noncomparative case series. PARTICIPANTS: Forty-two patients with ciliary body melanoma treated with iodine-125 brachytherapy. METHODS: Electronic chart review of ciliary body melanoma patients treated at Princess Margaret Hospital, University of Toronto, Toronto, Ont. Patients' demographics and clinical, management, and follow-up data, including brachytherapy-related complications, were reviewed. Outcome measures included rates of tumour control, eye preservation, systemic metastases, and brachytherapy-related complications. RESULTS: Median age at diagnosis was 58 years and median follow-up was 43 months. Ciliary body melanoma was asymptomatic in 55% of patients, whereas floaters or flashes were the main symptom in 33%. Median tumour thickness before brachytherapy was 5.2 mm and after brachytherapy was 3.3 mm. Radiation-induced cataract was the main complication in 55% of patients, radiation retinopathy in 24%, and neovascular glaucoma in 15%, which was controlled by topical treatment in half of the cases. Two patients developed metastases and 3 required secondary enucleation. CONCLUSIONS: Medium-sized ciliary body melanoma produced no or minimal symptoms on presentation in 88% of the patients. Iodine-125 plaque brachytherapy offered 98% tumour control at 43 months' follow-up. Radiation-related complications are generally manageable in most patients, which permits retention of the treated eye.

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.

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.

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.